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Re-evaluation of Benefits of BRCA1/2 Testing

California Cancer Medical Center, West Covina, CA

To the Editor: The article entitled "Benefits and Costs of Screening Ashkenazi Jewish Women for BRCA1 and BRCA2" by Grann et al¹ simulating the cost effectiveness of mutation testing for Ashkenazi Jewish women is interesting but would be improved if the following two additional factors were addressed. First, the statistics on the efficacy of breast screening rely on a general, rather than a high-risk, population. One reason for mutation testing is to begin breast screening earlier than usual for those at greatly increased risk, such as mutation carriers, since breast cancers commonly occur before age 40 in mutation carriers. If a simulation were performed using statistics on carrier women beginning at age 30, we believe the cost effectiveness of mutation testing would be enhanced, as well as the efficacy of screening as a viable option in carrier women.

Second, the authors allude to the proportion of Ashkenazi women who test negative for the three frequent mutations yet have a substantial personal and/or family history of breast and/or ovarian cancers. Many unique mutations are found in some of these Ashkenazi families, as are found in breast cancer families in general. Many Ashkenazi women with presumed mutations have not yet had the specific mutations identified. We strongly urge counseling for such families, to emphasize that failing to identify a mutation, even with complete sequencing, is not equivalent to not having a mutation, unless the causative mutation in the specific family has already been characterized.

REFERENCES

1. Grann VR, Whang W, Jacobson JS, et al: Benefits and costs of screening Ashkenzai Jewish women for BRCA1 and BRCA2. J Clin Oncol 17:494-500 1999[Abstract/Free Full Text]

Response

Herbert Irving Comprehensive Cancer Center, Columbia-Presbyterian Medical Center, New York, NY

In Reply: Drs Knell and Presant call attention to two important points in our recent publication in the February 1999 issue of the Journal of Clinical Oncology.¹ In a previous study,² we modeled the cost effectiveness of prophylactic surgery compared with surveillance for 30-year-old women who are mutation carriers. In the present study, our model indicated that in an Ashkenazi Jewish population with a 2.5% incidence of three specific mutations (not the general population with a mutation risk of less than 0.2%), 30-year-old women who intended to take appropriate preventive interventions if they tested positive for BRCA1/2 would benefit from prophylactic surgery. The model also indicated that waiting to have the surgery would reduce the benefit (increase the cost per life-year saved).

We focused our analysis on women with one of the three Ashkenazi Jewish mutations and did not assume that "screening Ashkenazi Jewish women with a family history of cancer will have a higher yield than screening Ashkenazi Jewish women irrespective of family history." We certainly agree that women who test negative for these mutations may still have other mutations or risks of developing breast cancer. Although we did not address counseling, we certainly agree that it is necessary. We also agree that among women who have a strong family history of breast cancer not associated with a known mutation, a negative test result is no guarantee of average risk.

As newer mutations are described, we plan to incorporate them into our model.

REFERENCES

1. Grann VR, Whang W, Jacobson JS, et al: Benefits and costs of screening Ashkenzai Jewish women for BRCA1 and BRCA2. J Clin Oncol 17:494-500 1999

2. Grann VR, Panageas KS, Whang W, et al: Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients. J Clin Oncol 16:979-985 1998[Abstract]

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