To the Editor.—As a writer on the subject of BRCA1 and BRCA2 mutations,[1] I read the Consensus Statement "Recommendations for Follow-up Care of Individuals With an Inherited Predisposition to Cancer: II. BRCA1 and BRCA2"[2] with particular interest and find the recommendations inconsistent and troublesome.
The paragraph in the abstract headed "Conclusions" (page 997) states, "Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations."[1]
The paragraph headed "Mammography" (page 999) states, "There is a potential increased risk of breast cancer when mammography is started at an early age, and this risk may be greater in individuals with an inherited cancer predisposition than in women of average risk." Further, the authors state that for this population there is a "likelihood that mammography screening provides benefit, although there are no data to support this view."
The "Summary" (page 1002) in regard to "individuals with cancer predisposing mutations" states that "early mammography may cause additional risk."
I don't understand how, if the only data in relation to early mammography indicate that it may be harmful, the authors of this article can recommend it to a more vulnerable population.
Estelle Gilson
Bronx, NY
1. Gilson E. Jewish women and the breast cancer gene. Congress Monthly. March/April 1997;64:12-15.
2. Burke W, Daly M, Garber J, et al, for the Cancer Genetics Studies Consortium. Recommendations for follow-up care of individuals with an inherited predisposition to cancer, II: BRCA1 and BRCA2. JAMA. 1997;277:997-1003.
(JAMA. 1997;278:289-290)
To the Editor.—In the provisional recommendations for follow-up care of individuals with inherited predisposition to cancer,[1] annual mammography is recommended beginning between the ages of 25 and 35 years, based on "expert opinion" only.
This might have seemed reasonable but for the publication, 1 month later, of 2 reports in Nature[2, 3] and an accompanying commentary[ 4] which reveal that BRCA genes, acting as "caretakers," are of great importance in DNA repair. Consequently, a person lacking functional BRCA genes would be exquisitely sensitive to even small amounts of ionizing radiation.
Would an expert now want to subject these women to the hazard of mammography?
Jayant S. Vaidya, MS (Surg), DNB
Michael Baum, ChM, FRCS, MD
University College
London, United Kingdom
1. Burke W, Daly M, Garber J, et al, for the Cancer Genetics Studies Consortium. Recommendations for follow-up care of individuals with an inherited predisposition to cancer, II: BRCA1 and BRCA2. JAMA. 1997;277:997-1003.
2. Milner J, Ponder B, Hughes-Davies L, Seltmann M, Kouzarides T. Transcriptional activation functions in BRCA2. Nature. 1997;386:772-773.
3. Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature. 1997;386:804-810.
4. Kinzler KW, Vogelstein B. Gatekeepers and caretakers. Nature. 1997;386:761-763.
(JAMA. 1997;278:290)
In Reply.—We agree with Ms Gilson and Drs Vaidya and Baum that there is a potential risk from mammography for women carrying BRCA1 and BRCA2 mutations, but we believe there is a greater likelihood of benefit. Vaidya and Baum note recent publications indicating a DNA repair function for the BRCA1 and BRCA2 protein[ 1-3] and suggest that these observations raise questions about the use of screening mammography for individuals carrying mutations in these genes. While a defect in a DNA repair mechanism may increase the risk of radiation exposure, we believe it would be premature to conclude that individuals carrying BRCA1 or BRCA2 mutations will be "exquisitely sensitive to even small amounts of ionizing radiation." This research finding is preliminary and of uncertain clinical significance. It may mean that cancers associated with BRCA1 and BRCA2 mutations are more sensitive to radiation. Further, while mammography may pose risk, it also remains the most effective screening tool available for detection of early cancer.
Thus, the finding of a possible DNA repair mechanism for the BRCA1 and BRCA2 proteins underscored the importance of further research. Only with objective information about clinical outcomes will we be able to determine the true risks and benefits of mammography in genetically susceptible individuals. Until such data are available, clinicians must counsel patients regarding uncertainties in the surveillance measures available, including the possible risk of mammography. At the same time, individuals with an inherited susceptibility should be informed of screening options for which a benefit is likely, though unproven. We believe early mammography falls in this category. Our article was not intended to supplant the need for further research or to set arbitrary guidelines for care, but rather to provide recommendations based on current knowledge and to serve as a guide for a comprehensive informed consent process. It is likely that surveillance recommendations for genetically susceptible individuals will change as new information emerges. In the meantime, decisions about follow-up care must be made through a partnership between individuals at risk and their clinicians after careful consideration of the limited evidence available.
Wylie Burke, MD, PhD
University of Washington
Seattle
Mary Daly, MD, PhD
Fox Chase Cancer Center
Philadelphia, Pa
Judy Garber, MD, MPH
Dana-Farber Cancer Institute
Boston,
Mass
Jeffrey Botkin, MD, MPH
University of Utah
Salt Lake City
Mary Jo Ellis Kahn
National Breast Cancer Coalition
Richmond, Va
Patrick Lynch, MD, JD
University of Texas
Houston
Anne McTiernan, MD, PhD
Fred Hutchinson Cancer Research Center
Seattle, Wash
Kenneth Offit, MD, MPH
Memorial Sloan-Kettering Institute for
Cancer Research
New York, NY
Jeffrey A. Perlman, MD
Claudette Varricchio, DSN, RN
National Cancer Institute
Bethesda, Md
Gloria Petersen, PhD
The Johns Hopkins University
Baltimore,
Md
Elizabeth Thomson, MS, RN
National Human Genome Research Institute
Bethesda, Md
1. Kinzler KW, Vogelstein B. Gatekeepers and caretakers. Nature. 1997;386:761-763.
2. Sharan SK, Morimatsu M, Albrecht U, et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature. 1997;386:804-810.
3. Scully R, Chen J, Plug A, et al. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell. 1997;88:265-275.
(JAMA. 1997;278:290)
