We need to discuss among ourselves, friends, the ethics of providing
such potentially devastating news as that which could be disclosed concerning
BRCA1 status without adequate counseling support.
This issue cannot be addressed lightly; however, it is now clear
that the mythic Pandora is out of her box, and our abilities to quell
her, are, as a community, about to be sorely tested.
The German poet, Ranier Maria Rilke, whom I quote below, truly
loved all the women he ever met, and they him... Let us live up to his
spirit in the wise counsel that we bring those we
see as patients and clients.
--
Bert Gold, Ph.D. "If only we stay with that principle
University of California, San Francisco which counsels us always to hold
School of Medicine to the difficult, then that which
Department of Pediatrics now seems to us most foreign, will
Program in Medical Genetics become what we most trust and
(415) 476-2850 find most faithful." - R.M. Rilke
---------- Forwarded message ----------
Date: Tue, 09 Apr 1996 22:31:19 -0500 (EST)
From: GENETHICS@delphi.com
To: bgold@itsa.ucsf.edu
Subject: BRCA testing
Bert:
Not sure if you saw this. The simple truth is that while NIH, Collins, ELSI
and the whole establishment studied, re-studied and re-restudied the
obvious, nature took its course.
Hans
By GINA KOLATA
c.1996 N.Y. Times News Service
In the small world of geneticists in the forefront of studying human
disease, the researchers tend to know one another. So last year, after the
discovery that as many as 1 percent of Jewish women carry a mutated form of
a gene that might predispose them to breast and ovarian cancer, it was easy
enough for leading scientists and two major commercial testing labs to agree
informally not to offer the test to the general public.
The reasoning was that many questions remained about the risk posed by the
gene, about what, if anything, could be done to lessen the risk and about
whether widespread testing would do more harm than good.
Now, however, a private commercial institute that was not part of any
agreement to hold back on testing is offering the test to the public,
arguing that women have a right to know whether they carry the mutated gene
and that it is patronizing for scientists to say otherwise.
That decision, by Dr. Joseph D. Schulman, director of the Genetics and IVF
Institute in Fairfax, Va., to offer the test for $295 has outraged some
leading geneticists, raising the question of how, and by whom, the
dissemination of new genetic tests should be controlled.
But others are rooting for Schulman. Dr. Walter Nance, who is chairman of
the department of human genetics at the Medical College of Virginia in
Richmond and a past president of the American Society of Human Genetics,
said he thought that Schulman was ``doing us a service by goading the
community.''
Nance added: ``We have a test here that does have the potential of actually
saving lives. That being true, you've got to ask the question, How long can
you delay it? How long are you willing to delay it? Are you willing to go
through NIH grant cycles and apply for grants? Is that an appropriate way to
bring it to the public?''
The test is for a mutation of a normal gene called BRCA1. Researchers first
found that women of Ashkenazi Jewish descent whose close relatives developed
breast and ovarian cancers and who inherited this mutated version of the
gene had as much as a 90 percent risk of developing breast cancer and a 40
to 50 percent risk of developing ovarian cancer.
Then, last September, investigators published a paper showing that 1 percent
of Ashkenazi Jewish women, those of Central or Eastern European ancestry,
had the mutated form of the BRCA1 gene. That and other reports in scientific
journals were sufficient for Schulman's institute to develop the test.
But the researchers cautioned in their paper that without further studies,
they could not say for certain that all the women with the mutated gene were
at risk for cancer. That advice was taken even more seriously because one
author of the paper was Dr. Francis S. Collins, the influential director of
the Human Genome Project at the National Institutes of Health.
Among the reasons for the scientists' caution was the possibility that the
mutated gene is not dangerous in women who do not have a strong family
history of breast cancer. For example, the gene might require mutations in
several other genes to wreak its damage, and those other mutations might be
manifest in relatively few families, those in which woman after woman has
been stricken by breast or ovarian cancer.
Furthermore, even if a woman with the faulty gene had close relatives with
breast cancer and clearly had a high risk of cancer, it was not clear how
knowledge of that risk could help her protect herself. Would frequent
mammograms be enough? Should she have her breasts and ovaries removed and,
if so, what guarantee of safety would that provide?
In the face of these uncertainties, said Dr. Neil A. Holtzman, a geneticist
at the Johns Hopkins Medical Institutions, ``there was an agreement among
geneticists to go slowly.'' They agreed, he said, that ``the test should be
scientifically and clinically evaluated before it becomes routinely
available'' and used only in research until then. In one large federal
study, about 5,000 Jewish men and women will be tested but will not be told
whether they have the gene.
Holtzman is chairman of a federal task force on genetic testing that
recently released an interim report stating when genetic tests should be
used. He said the BRCA1 test would not meet the criteria for making it
available to the public.
But Schulman was not involved in these informal discussions about the test
and said he considered them ``mind boggling.'' Others might have agreed to
hold off on BRCA1 testing, he said, but ``we were not part of such an
agreement.'' He said he felt very strongly that Jewish women had a right to
know whether they have the mutation and that it was patronizing for
geneticists to tell them to wait while research continued.
nn
Schulman gave no credence to the hypothesis that the mutated gene might pose
little risk in women without a family history of breast cancer. The
mutation, he said, involves a deletion of genetic material that destroys the
functioning of a tumor suppressor gene. For that reason, he said, ``it is
genetically and medically impossible that this mutation is insignificant in
people with no family histories'' of cancer.
He also said that despite the qualms of some geneticists about whether
prophylactic mastectomies reduce the cancer risk, ``there isn't a single
rational person in the world who really believes that.''
``What's indefensible to me is not to give people a choice,'' he added.
``There are fantastic numbers of people who want to know.'' One of them is
his wife, Dixie, a scientist who works at the institute. She is Jewish, and
her mother, grandmother and great-grandmother all had breast cancer. She
wanted to know whether she had the BRCA1 mutation but found nobody who was
offering a test outside a research protocol, she said.
Independently of his wife's situation, Schulman and his colleagues at the
institute decided to offer BRCA1 testing to Jewish women earlier this month.
They began by offering it to women at the institute and to Mrs. Schulman's
mother. Almost all said they wanted the test, and of the 16 women tested, 2
had the mutated gene: Mrs. Schulman and her mother.
Mrs. Schulman, who is 38, said she had not really been surprised to learn
she had the mutated gene. Her family history of breast cancer is so strong
that her doctor had advised her at age 18 to have both breasts removed
prophylactically. She refused then, she said, but she is going to do that
now. She also said she was likely to have her ovaries removed before she
reached menopause.
``Now I know what my alternatives are,'' Mrs. Schulman said.
Schulman added, ``We thank God we have this test result.''
Schulman has supporters. ``You can't hold back advances because you want
everybody not to feel emotionally upset,'' said Dr. Christine Berg, director
of breast radiation therapy at the Vincent Lombardi Cancer Center at
Georgetown University. ``I think that saying you're not going to do the
testing is very restricting and patronizing.''
Berg added that the situation with the BRCA1 test contrasted sharply with
how a nongenetic blood test for prostate-specific antigen, a marker for
prostate cancer in men, had been handled, even though it has perhaps more
drawbacks and uncertainties than the BRCA1 test.
The PSA test can detect tiny prostate cancers, but no one can say whether a
man's tiny tumor will become life-threatening. To play it safe, most men
with such tumors have their prostates removed, a treatment that doctors hope
will protect the men but that has never been proved to be effective. Most
men who have their prostates removed end up impotent and incontinent.
Yet, Berg said, ``the urology community has embraced the PSA test
wholesale.''
In contrast, the researchers who agreed not to test for the BRCA1 gene say
they are outraged that the test is being offered at Schulman's institute.
Dr. Michael M. Kaback, a geneticist at the University of California in San
Diego, said: ``Schulman is an entrepreneur. He masks it in all this talk
about giving people the right to make their own decision, and he's convinced
himself that he's doing the right thing, that people have to have this
information. Fine, but `first, do no harm.' The conflict is, every time he
runs a test, he generates profits.''
Kaback and others say that if the test is used inappropriately, it could
cause fear in the face of uncertainty and create problems with insurance or
even employability.
``It's clearly premature to be jumping on this thing,'' Kaback said. ``Just
because a test exists doesn't mean that everybody has to know about it and
have, quote unquote, informed choice.''
Holtzman said he did not know what steps geneticists could take.
``We have a number of options,'' Holtzman said. ``One is to state the
principles. Obviously, that's not enough. Another is an industry code. Well,
here are people like the Genetics and IVF Institute who may ignore it. Then
there are professional guidelines. Well, we've got professional guidelines,
and they're not working.'' That leaves the Food and Drug Administration, he
added, which has declined to regulate individual laboratories that are
marketing services like genetic tests.
