Recent dramatic advances in the understanding of inherited susceptibility to several common adult-onset cancers have made possible the identification of individuals who may be at significantly increased risk of developing malignant disease. These advances may translate into some of the first opportunities for cancer prevention.
Recent dramatic advances in the understanding of inherited susceptibilityto several common adult-onset cancers have made possible the identificationof individuals who may be at significantly increased risk of developingmalignant disease. These advances may translate into some of thefirst opportunities for cancer prevention.
The most notable examples of successful gene isolation that holdsuch promise include identification of the genes for inheritedcolon, breast, ovarian, and thyroid cancer. However, these samesuccesses open a Pandora's box of predictive testing that health-careproviders have not had to consider previously. Concerns aboutthe possibility for error or misinterpretation, costs, potentialdiscrimination, financial vulnerability from loss of insuranceor employment, psychological harm, and uniform accessibility haveall been raised in the international debate on how to use thesenewly discovered genes to best advantage. Dr. Holtzman raisesthe question, "Are we ready to screen for inherited susceptibilityto cancer?" and concludes, based on many of these concerns,that we are not ready.
Arguments Against Screening
The arguments against screening put forth in his article centerlargely on our current lack of knowledge in the following areas:(1) the predictive value of the test, which is decreased whennot all mutation carriers develop disease and when the age ofonset and clinical course of the disease cannot be accuratelydetermined; (2) the effectiveness of interventions being offered;(3) the potential risks of screening; and (4) the cost-effectivenessof screening programs.
Dr. Holtzman argues that mutations in the currently known cancersusceptibility genes have been studied in only a small numberof severely affected families, that the role of these same mutationsin the general population remains unknown, and that quality oflife and long-term survival may not be affected in individualsundergoing screening. He further argues that the use of screeningin children and pregnant women is of even more questionable benefit,and that there is potential for exploitation by the entry of corporateconcerns into the genetic testing arena, in the form of aggressivemarketing practices and pricing that may place such testing beyondthe reach of many individuals. Dr. Holtzman thus urges restraintin offering genetic testing for cancer susceptibility as a screeningtool and suggests that screening efforts be limited to pilot studieslinked to randomized clinical trials of prevention strategies.
Screening vs Testing: A Key Distinction
The critically important concept in evaluating the concerns raisedby Dr. Holtzman is the distinction between screening and testing.By definition, "screening" denotes the application ofa test to a large population, in this case, the American public(or at least American women with regard to breast and ovariancancer). Examples of screening tests in current use include mammograms,Pap smears, and stool occult blood tests. These tests have incommon low cost, ease of performance, minimal risk, and the abilityto detect potentially curable disease. They have been recommendedat regular intervals for all men and/or women over a specifiedage in the United States.
In contrast, the term "testing" generally is used toindicate the performance of a test for specific indications, suchas breast ultrasound to further define a previously detected breastmass, colposcopy to examine the cervix of a woman with atypicalcells on Pap smear, or colonoscopy to evaluate an individual withoccult blood detected in stool. These tests are not recommendedfor routine screening of asymptomatic individuals, as they maybe expensive and/or inconvenient and would result in a negativecost-benefit ratio if indiscriminately applied to a large population.Nonetheless, they are extremely valuable tools when used in theproper setting. Genetic predisposition tests should be evaluatedwith this same distinction in mind.
I agree with Dr. Holtzman that we are not ready to screen peoplefor inherited susceptibility for cancer, and further suggest thatwe may never be. However, testing individuals with defined risksfor inherited susceptibility to cancer clearly offers great promise.To withhold such testing because we are not ready for screeningwould be a great disservice to members of cancer-prone familieswho have, in many cases, been trying to understand and deal withthe early loss of multiple family members spanning several generations.
To members of such families, as well as to patients who developcancer at an age significantly below the median age of onset inthe general population, we can offer explanations, reassurance,and hope. In addition, from long-term follow-up of these patients,we can derive answers to currently unanswerable questions aboutintervention. Finally, these individuals will pave the way forinsurance reform and antidiscriminatory legislation. While decisionson the advisability of population-based screening clearly mustawait the results of the pilot studies proposed by Dr. Holtzman,we must not curtail efforts to educate health-care providers andconsumers about the power and the pitfalls of predisposition testingfor defined individuals, the established need for associated counseling,and the selection of appropriate testing candidates.