Correspondence

Genetic Screening for Breast Cancer

N Engl J Med 1996; 334:1200-1201May 2, 1996

Article

To the Editor:

In his editorial (Jan. 18 issue),1 Dr. Collins discusses many of the issues surrounding the presymptomatic testing of women for BRCA1 mutations when their families are at high risk for breast and ovarian cancer. Because of the high frequency of the 185delAG mutation in Ashkenazi Jews2 and because this single mutation accounts for a large proportion of hereditary cases in the population,3 we offer testing for the mutation at McGill University and the University of Toronto. We explain that only a positive test is informative and that once a positive case is identified in the family, we can accurately predict the carrier status of the other women in the family. When possible, we use both linkage analysis and direct mutation information in the risk analysis. Because we have been able to inform women who were scheduled for prophylactic surgery that their surgery was not indicated, clearly for these women the test was clinically useful and not premature.

We believe that under these circumstances the sensitivity and specificity of the test are sufficiently high and that predictive testing is accurate. Fortunately, in Canada we are not currently constrained by a system of private health insurance or restricted access to appropriate follow-up care. When genetic testing for cancer is discussed, we believe that it is necessary to distinguish between issues of scientific validity, which are universal, and those of social policy, which differ among countries.

David S. Rosenblatt, M.D.
William D. Foulkes, M.B., B.S., Ph.D
McGill University, Montreal, QC H3G 1A4, Canada

Steven A. Narod, M.D.
University of Toronto, Toronto, ON M5G 1N8, Canada

3 References

1. 1

   Collins FS. BRCA1 -- lots of mutations, lots of dilemmas. N Engl J Med 1996;334:186-188
   Full Text | Web of Science | Medline

2. 2

   Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 1995;11:198-200
   CrossRef | Web of Science | Medline

3. 3

   FitzGerald MG, MacDonald DJ, Krainer M, et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 1996;334:143-149
   Full Text | Web of Science | Medline

Author/Editor Response

Dr. Collins replies:

To the Editor: Rosenblatt et al. correctly point out that the technical and laboratory challenges associated with testing for the 185delAG mutation of BRCA1 in Ashkenazi Jewish women are reduced considerably, as compared with those encountered in heterogeneous populations in which a wide variety of mutations can be expected. They also point out that at-risk Canadian citizens face a smaller likelihood of genetically based discrimination in health care than their U.S. counterparts. However, the possibilities of discrimination in employment and life insurance remain sufficiently real in Canada that they should be disclosed to any woman considering BRCA1 testing.

But scientific validity and social policy are not the only issues surrounding BRCA1 testing. The current uncertainty about the appropriate medical care of mutation carriers presents a major challenge to patients and physicians. Few would deny the usefulness of a negative test when other family members have known BRCA1 mutations, but a patient contemplating testing must also understand clearly the personal consequences of a positive test. As several observers have pointed out,1,2 carriers of a BRCA1 mutation are faced with difficult and uncertain choices about medical or surgical options to reduce the risk of breast cancer and ovarian cancer, and convincing data on efficacy are not yet available.

Faced with these uncertainties, the Hereditary Susceptibility Working Group of the National Action Plan on Breast Cancer, a public–private partnership designed to eradicate breast cancer as a threat to the lives of American women, recently concluded: “The lack of scientific knowledge about BRCA1 and BRCA2 makes clinical uses of mutation testing premature outside of research protocols.”3

It is likely that Rosenblatt et al. are offering potentially useful information to ashkenazi women at risk. But would the dual goals of protecting human subjects and furthering scientific knowledge not be better served by carrying out these studies in the context of a research protocol approved by an institutional review board?

Frances S. Collins, M.D., Ph.D
National Center for Human Genome Research, Bethesda, MD 20892

3 References

1. 1

   Biesecker BB, Boehnke M, Calzone K, et al. Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. JAMA 1993;269:1970-1974
   CrossRef | Web of Science | Medline

2. 2

   Hoskins KF, Stopfer JE, Calzone KA, et al. Assessment and counseling for women with a family history of breast cancer: a guide for clinicians. JAMA 1995;273:577-585
   CrossRef | Web of Science | Medline

3. 3

   Statement on hereditary susceptibility testing for breast cancer. Washington, D.C.: National Action Plan on Breast Cancer, March 1996.
   

Citing Articles (2)

Citing Articles

1. 1

   Louise Bouchard, I Blancquaert, F Eisinger, W.D Foulkes, G Evans, H Sobol, C Julian-Reynier. (2004) Prevention and genetic testing for breast cancer: variations in medical decisions. Social Science & Medicine 58:6, 1085-1096
   CrossRef

2. 2

   (1996) Pitfalls of Genetic Testing. New England Journal of Medicine 335:16, 1235-1237
   Full Text