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To: HUM-MOLGEN@NIC.SURFNET.NL
Subject: ETHI: BRCA testing
From: GENETHICS@delphi.com
Date: Tue, 9 Dec 1997 14:11:09 -0500

Just one response to the recent posting on BRCA screening. After this post
was received by HUM-MOLGEN, there was a press report of a Department of
Defense/Mayo Foundation study which found an 85-90% reduction in breast
cancer incidence among 1000+ women who had had prophylactic mastectomies
between 1960 and 1993.

The ETHI topic welcomes submissions of interesting queries, observations or
just plain musings on the social ethical and legal aspects of genetics.

Hans Goerl
ETHI editor
*****************************************************************************
**************


From: "Mark Robson <Robson_Mark/mskcc_HG@MSKMAIL.MSKCC.ORG>

     I would like to briefly respond to Dr. Krul regarding his opinions on
     the utility of BRCA1/2 testing. I agree that BRCA1/2 testing is not
     suitable for population screening, both because of expense and because
     of issues of test specificity. However, in families whose history
     suggests the presence of a susceptibility allele, testing can be
helpful      for several reasons. First, there are differing degrees of
"increased      surveillance," and the finding of a BRCA mutation may guide
a woman in      determining the intensity of her follow-up. As an
alternative to increased      surveillance, women can and do elect
prophylactic surgery. Whether this      approach is "better" than
surveillance remains a research question. While I      agree that cancers do
occur after prophylactic mastectomy (or      oophorectomy), evidence is
accumulating as to the efficacy of the      procedures in substantially
reducing risk, even in high-risk cohorts. I am      completely unaware of
prophylactic surgery having been performed in the s      setting of a
"false-positive" BRCA mutation analysis. If Dr. Krul has      knowledge of
such cases, I would encourage him to submit them for      peer-review, as
this information would be of importance to the clinical      cancer genetic
community. Until such peer-review has taken place, I would      encourage
him and others not to propogate unsubstantiated rumors.

     Next, BRCA mutations confer a risk of second malignancies, particularly
     ovarian cancer but possibly also colon and prostate. Surveillance for
these      malignancies is NOT usually performed in a woman with a simple
family      history of breast cancer. Accordingly, women found to have a
mutation may      well embark upon a different surveillance program than
they would have in      the absence of the information.


     Finally, women (and men) from hereditary breast or breast-ovarian
families      often suffer considerable anxiety as a consequence of their
family      histories. In a family with a documented mutation, the finding
that an      individual does not harbor that mutation signifies that her
breast and      ovarian cancer risk is most likely that of the general
population. This      allows her to follow population screening guidelines
rather than intensive      surveillance guidelines, and often provides
significant relief from      anxiety.


     We have much to learn about inherited susceptibility to breast and
ovarian      cancer in general, and BRCA1/2 in particular. However, the
information      gained from testing is already proving helpful to selected
families when      performed with informed consent in the context of
appropriate genetic      counseling. The major potential barriers to the
beneficial application of      genetic testing are not those described by
Dr. Krul, but social concerns      such as insurance and employment
discrimination.


     Mark Robson, MD
     New York, NY
*****************************************************************************
***************

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