2

Families and genetic testing: the case

of Jane and Phyllis
Anneke Lucassen

We share much of our genetic make-up with members of our biological family.
This means that genetic information about one person is also sometimes, to a
greater or lesser extent, information about that person’s relatives. A genetic
test can sometimes therefore diagnose or predict disease not only in the
individual tested but also in his or her biological relatives.
The familial nature of the information produced by genetic tests raises
questions about the legal and ethical obligations of healthcare professionals
to disclose or withhold genetic information about patients to their at-risk
relatives. Such questions are brought into sharp focus by clinical genetic
situations in which different members of the same family are all ‘patients’
of one clinician but each attends the clinic independently with separate issues
and agendas that need to be addressed. In such situations each patient is owed
a duty of care by that clinician, who may feel pulled in different directions by
the differing needs of the family members, and may feel unclear about how to
prioritise each. Such questions are particularly difficult when family mem-
bers are in conflict but they also arise when members have simply lost touch
with each other. In such cases, there can be an ethical conflict between
preserving the confidentiality of one patient on the one hand and the right
of other family members to know information about their genetic status and
risk of disease on the other.
Such problems are not new. The speciality of clinical genetics has always
dealt with families, and with the tensions or lack of contact between family
members. Different opinions within families are certainly not new. However,
in the past, and until relatively recently, the only advice geneticists were able
to provide consisted largely of estimates of risk of inheriting or transmitting
a particular genetic condition. With the advent of genetic testing for an
increasing number of conditions, it is now possible in some cases to infer
or produce reasonably accurate information about actual inheritance.
In some cases, the ability of a genetic test to deliver useful prognostic or
predictive information to an individual patient is dependent on the prior
Case Analysis in Clinical Ethics, ed. Richard Ashcroft, Anneke Lucassen, Michael Parker,
Marian Verkerk, Guy Widdershoven. Published by Cambridge University Press.
# Cambridge University Press 2005. 7
8 Anneke Lucassen

identification of the causative genetic alteration in that particular family. This

is usually only possible in a living family member who is actually affected by
the condition. So this means that an unaffected member of a family who
wants to know whether they have inherited a condition or a tendency towards
a condition may need the co-operation of an affected relative in order to
make an accurate test possible. This introduces another familial element into
the practice of genetics.
In many families there is a willingness – and even an eagerness – to share
genetic information of this kind, but in others conflict or separation results in
situations where the clinician has to choose between preserving the confi-
dentiality of one relative and making predictive genetic testing available to
another. In such cases, where an accurate and useful test is only possible if
the familial mutation has been identified, such conflicts can be difficult to
resolve.
The following clinical case (see also Appendix I) highlights just such a
conflict. The case, which is a construct composed from several cases I have
encountered as a clinical geneticist, is also informed by a number of different
stories told to me while seeing families clinically.

Jane’s story

I have always known that most women in my family develop breast cancer,
usually at a young age, and that they eventually die from it. I suppose when
I was in my teens and twenties I knew it but it seemed remote to me. Once
I reached my thirties and had my own two daughters things started to feel
different. I worried more about developing cancer and about not being there
for my girls. I worried that they too might have got our family curse. While
my girls were little I always had other things to think about, but now that
they’re a bit older I think about it all the time.
The worries often loom large in the early hours when I lie awake fretting.
My husband eventually persuaded me to see the doctor. He said I should go
to see her because I didn’t know what could be done these days and that
treatments must be different from when mum and her mum developed
cancer. At about the same time I also saw an article in the newspaper about
genetic testing for women like me and I went to ask my GP about it. She was
very good and gave me a lot of time. She talked a bit about mammograms and
how to examine my own breasts. She didn’t know much about genetic testing
but said she’d refer me on to a specialist.
After several weeks of waiting I was sent a family history questionnaire to
fill in. It asked about details of the cancers in my family, which hospitals my
relatives had been treated at, how old they were and all sorts of other
questions. I spent days filling it in. I found it hard and upsetting to complete.
 Families and genetic testing: Jane and Phyllis 9

After several months I finally got an appointment to see the specialist. She
told me that it did sound like there was a rogue gene in my family that could
explain all the cancers. She gave me lots of information, most of which I don’t
remember now, but I do remember her saying that there is a possibility that
I may not have inherited the rogue gene. My mum had two copies of the gene
and only one was faulty. When mum had us, she only passed on only one
copy, either the normal one or the faulty one, so it was ‘heads or tails’ each
time she had a child. If I didn’t get it, I’m unlikely to get cancer young; if I did,
then I probably will. The only problem is that we can’t really tell whether
I have or haven’t got the relevant gene as the tests aren’t yet very good. In
order for me to have an accurate test, the researchers would first need to find
the particular rogue gene in an affected person in my family since each family
can have a slightly different type of rogue gene. For the test to be accurate in
me, they need to know exactly which gene fault they are looking for before
they test me for it. If they tested me without this first bit of information, and
I tested negative, it could mean that I hadn’t got mum’s rogue gene but, and
this was the big but, it could also mean that I had got it but the researchers
had not been able to find it because their tests aren’t good enough to pick up
all the different types of gene faults.
If they knew what to look for, they’d be able to offer me a straight ‘yes’ or
‘no’ answer; but if they don’t, a test isn’t really going to help me to decide not
to have an operation. Since all the women in my family seem to die from cancer
rather quickly there is no-one who is affected that I can ask to undertake this
first stage test. Without this, testing me seems like a bit of a ‘don’t know’ test.1
At the end of the meeting, the doctor said it might help if I got some more
information about mum’s relations. I think that Great Uncle Stan emigrated
to Australia in the 1970s and the doctor said finding out if maybe he had had
any daughters with breast cancer who were still alive could be helpful. I know
very little about mum’s family really as I was only 21 when she died. I was her
baby and I think she didn’t want to tell me things that she thought might
upset me. I did know Auntie Phyllis was still alive although I hadn’t seen her
since mum died.
When I asked him, Uncle George told me Phyllis still lived in the same
house, but when I finally got in touch with her she didn’t really have any more
information. She’s a rather grumpy thing. She and mum had some row over
money and she went on about mum being the spoilt one. I found the visit
rather depressing. She looked old and not very well but she’s only in her 50s.
By the time I went for my second appointment at the genetics clinic I’d
done loads of reading around the subject and talked to a woman who ran a
support group who had a very similar story to mine. She had had an
operation called a prophylactic mastectomy, which removes almost all of
your breasts so that you can’t develop cancer in them. The genetics doctor
said that there was evidence to show that women like me who had this
10 Anneke Lucassen

operation probably did better than women who just examined themselves
and had mammograms. To be honest, I was already pretty convinced this was
the way to go before that, especially as my husband also thought this was a
good idea, but also because genetic testing in me probably wasn’t really going
to be that helpful for a few years yet. I just thought, if I have the operation
then I can stop worrying. I was so fed up of having this gnawing anxiety
constantly in the back of my head.

Phyllis’s story

I knew I was doing pretty well to get to 50 without developing cancer, all the
other women in the family had got it much before that, but when I felt the
lump in my breast I knew straight away that it was cancer.
Everything moved very quickly – before I knew it I’d had the operation and
I was told I was ‘doing very well’. The oncology doctor looking after me was
young and very energetic. He said that because I had so many relatives with
cancer that the cancer might be due to something I’d inherited. He said a
blood test might show this. If it did show it then he would probably suggest
a different treatment than if it didn’t. I don’t think he ever asked whether
I wanted the test, he just took the blood sample. About a year later when I’d
clean forgotten all about it, I got a letter from him saying that the test had
found something and that he’d send me on to some genetic people to talk
about it. To be honest I found the genetic people were rather wishy-washy.
They never seemed to have a clear ‘yes’ or ‘no’ answer to my questions. They
said the result was a faulty gene, but that there wasn’t good enough evidence
to show that it should alter my treatment in any way, especially as I was now
well. They were more interested in my relations who hadn’t got cancer, which
was a bit of a cheek. I told the doctor how I’d nursed my mother and my sister
when they were dying. Neither of them thanked me for it. My sister and I had
a huge row about money just before she died – it was dreadful. I wasn’t even
mentioned in her will and the family completely ignored me afterwards.
I don’t feel I owe them anything. So no, I wasn’t happy with them letting
others know of my test result. I’m not in touch with them. It is my result, not
anyone else’s business. I’m fed up with being blamed for anything that goes
wrong in our family.

The general practitioner’s story

I first realised there was a problem when I got the letter from the clinical
geneticist. Phyllis wasn’t happy to divulge the result of genetic testing to her
family members, but in theory the result could be used by her niece, Jane, to
 Families and genetic testing: Jane and Phyllis 11

decide whether to have a prophylactic mastectomy or not. Without the result

Jane might have the operation unnecessarily, i.e. undergo it when in fact she
hadn’t inherited the cancer trait.
Of course, it wouldn’t have been so much of an issue for us had not both of
the two women been registered at our practice. My partner looks after Phyllis,
and I had met Jane on several occasions. We discussed it at a practice meeting.
My partner felt very strongly, and I think I agree with him, that neither we nor
anyone else, should break Phyllis’s confidentiality. She specifically said that
she does not want anyone to know. I think her main reasons are that she
would feel blamed by the family and I think that is reasonable.
General Medical Council guidelines say we should only break confidentiality
in a very serious or life-threatening condition. From what I understand, there
is not enough evidence to show clearly that prophylactic bilateral mastectomies
in Jane will reduce her chance of dying from breast cancer. Plus, it’s a major
and mutilating piece of surgery. I think she should just have regular screens.
My partner wondered why they couldn’t just test Jane for the gene fault that
they’ve found in Phyllis but without letting Phyllis know. I thought that was
probably a good way round. However, when I spoke to the genetics team they
indicated they had already explained to Jane – before they knew she and
Phyllis were related – that genetic testing wasn’t going to be helpful without
first having obtained the results of this same test on an affected family
member. Going back to Jane and changing that story would mean she’d be
able to infer things about Phyllis’s state of health.

The oncologist’s story

I attended a one-day seminar on advances in genetics and oncology a few

months before I first saw Phyllis, and this suggested that the treatment of
hereditary breast and ovarian cancer should be more aggressive than that of
sporadic cancer. I had this in mind when I sent off for the BRCA genetic test
on Phyllis (see Appendix II). She had consented to lots of investigative blood
tests as part of her diagnosis and treatment. I did not specifically discuss with
her the consequences of a genetic-test result for her family but that was not
my prime reason for performing the test – I wanted clarification on the
nature of her cancer. I have discussed the case with the clinical genetics
department and I now realise the genetic-test result has created difficulties.
Partly this is because of the low sensitivity of current testing, which is the
ability of a test correctly to screen gene-free individuals as negative.
Sensitivity is likely to improve in the future and when it does we will no
longer be dependent on results in one relative in order to undertake a test of
adequate specificity in another but it may of course be that similar dilemmas
will continue to arise in other genetic tests.
12 Anneke Lucassen

I can see that a genetic test is unusual because it can reveal information
about people other than those who actually have the test. Nevertheless,
ultimately I am responsible for the patient in front of me and if I have
evidence to suggest that my treatment of a cancer might be different depending
on the result of a genetic test then I think it appropriate to do that test
without having to seek the consent of other relatives who might also have an
interest in the result of that test. I do think it is appropriate for the geneticists
or counsellors to try to facilitate discussion between the two women. But at
the end of the day we shouldn’t have to consider the effects of a test on all
family members before proceeding with it, that’s just not practical or feasible.

The geneticist’s story

Jane attended the genetics clinic asking for a genetic test to see whether she’d
inherited her family trait for breast cancer. She’d read about genetic testing in
a magazine, but unfortunately the magazine had not spelt out the current
limitations of such testing. I told her that at present genetic testing for breast
cancer susceptibility is a two-stage process. In order for her to have a test that
tells her whether or not she has inherited a familial trait for breast cancer
(a predictive test) a first-stage test must be done on an affected family member
which will then enable a subsequent test on Jane herself to provide a definitive
yes/no answer (a diagnostic test).
Without a predictive test on an affected family member with breast cancer
that would be able to identify a causative or pathogenic mutation, a diag-
nostic test on Jane would have a very low sensitivity. This is because there are
at least two and probably more different genes that, if mutated, cause a high
risk of breast cancer. Hundreds of different mutations in these genes in
different families have been described. Current technologies can at best
pick up 70–80% of these mutations and in fact most testing in this country
detects a smaller percentage. This means that testing Jane directly is unlikely
to help her decide against a prophylactic mastectomy: a negative test would
not usefully distinguish between whether the mutation was not present (that
she has not inherited it) or whether it had simply not been identified due to
the limitations of current techniques. So a ‘negative’ result could not reliably
be taken to mean she had a reduced chance of having inherited the cancer
trait. However, a negative predictive test, if the diagnostic test had already
shown up the relevant mutation in Jane’s family, could accurately tell her that
her risk of breast cancer is now roughly the same as that in the general
population. Although this risk is roughly equal to a 1 in 10 chance in a
woman’s lifetime, sporadic cancers are usually late-onset and Jane could
therefore be reassured that her chances of developing young-onset cancers
seen in her family were extremely low, and we would advise against prophylactic
 Families and genetic testing: Jane and Phyllis 13

surgery. Predictive testing, as the magazine suggested, can be highly accurate, but
it is not informative if we don’t know which particular mutation we’re looking
for, and for that we need to find the mutation in an affected relative.
When I first met Jane she told me that all her relatives who had had cancer
were long since dead. Only later were we referred Phyllis, together with her
BRCA1 mutation result. This doesn’t happen that often, as we usually initiate
testing, but there are a few keen oncologists around who feel they might as
well send the test off if there is a strong family history. When this has
happened before there hasn’t usually been an issue about disclosing the result
to other family members since that is usually the main motivation for doing
the test. However, it is clear that the test result does also have implications for
Phyllis. It now gives her a clearer risk of ovarian cancer (up to a 60% chance
in her lifetime) and she may want to consider a prophylactic oophorectomy
to reduce her risk. If and when there is good evidence to suggest that the
treatment of gene-mutation-related cancers is different from that of sporadic
cancers, then I guess this situation will happen more often.
Usually, in cases where the diagnostic test has revealed a pathogenic mutation,
we’d leave the onus up to the person we see to contact their relatives and
inform them of the possibility of a predictive test. We feel we cannot directly
approach people who have not been referred to us. Of course we have no idea
how often such subsequent communication simply never takes place, leaving
people with a large degree of uncertainty, or even ignorance, about whether
or not they will develop young-onset breast cancer, which could, in theory, be
removed by a predictive genetic test. But we also do not know how many
women in this situation would want to know the genetic nature of the
condition in an affected family.
In this case, however, the two women were referred to us independently
and were both patients of the regional genetics service. I saw Jane and my
colleague saw Phyllis. It was not until a case conference that we realised the
two were related. By that time I’d spelt out the problems of genetic testing to
Jane which included an explanation of the fact that she couldn’t have a useful
predictive test unless we could first find the pathogenic mutation in an
affected relative. She’d even sought Phyllis out and spoken to her but
Phyllis hadn’t told her about her cancer or her test result. We couldn’t
therefore fudge the issue with Jane. She’s an intelligent woman; if we’d
suddenly said ‘Oh we can do a test after all’ – and just looked for the mutation
that we knew to be present in Phyllis – then Jane would have realised that we
must have information from one of her relatives and she’d probably have
been straight round to Phyllis.
I can see that it would be breaking Phyllis’s confidentiality to tell Jane. It’s
true that there is not yet any research evidence that clearly shows that women
who are likely to have one of these dominant breast-cancer genes should
have prophylactic bilateral mastectomies recommended to them. But there
14 Anneke Lucassen

is accumulating evidence that the lifetime risk of cancer following such an

operation is significantly reduced; short-term follow-up studies of these
women have shown that the cancer incidence is much lower in these women
than in the same-risk women who are just screened regularly. However, there
are not yet any data that suggest the mortality from breast cancer is reduced if
these women have such an operation. Such data may never be collected, partly
because the number of families are small and partly because randomisation of
studies might be difficult; anecdotally, women may either want or not want
such a major operation based more on their family’s experience rather than
on a risk figure that we provide for them.
When women have seen many members of their family die from breast
cancer, I think it not unreasonable to discuss such an operation as there is
enough evidence to suggest it is likely to be of benefit. If there was absolutely
clear evidence of benefit then I would find it easier to argue that breaking
Phyllis’s confidentiality is justified in order to prevent serious harm, i.e. an
unnecessary major operation. Since we do not direct women to have such an
operation when we clearly know they have a gene mutation (but only suggest
it as an option) can we say that breaking confidentiality is justified in this
case? Or should we advise Jane that there is not enough evidence for surgery
in any case? Even without these ambiguities I feel it is difficult to know how to
proceed when there is such a direct clash of interests between family members.
Clearly, negotiation might help but my colleague has tried hard to suggest to
Phyllis that it would be in the interest of her family to disclose (and that in
itself is difficult to do without breaking Jane’s confidentiality), but she just
doesn’t see it as in her best interest. Phyllis feels she would be blamed and
stigmatised. She’s a sad and isolated woman who shouldn’t be bullied into
doing something she thinks will bring her harm.
Jane is pretty much decided on having prophylactic mastectomies, yet
there is a 50% chance this will be unnecessary. This is, however, a situation
she is only prepared to tolerate because she thinks there is no way of getting a
more accurate risk figure. But we know this is not the case. How would she feel
if in years to come she found out that she had never needed the operation and
that we had had the information available at the time to show this yet we
allowed her to proceed with major surgery regardless? I feel that in these
situations, Phyllis’s test result really belongs to her whole family, not just to
her. She has information that is highly relevant to Jane, yet she is withholding
it. I think that we should make it a condition of testing in the first place, that it
will be all right to use the test result for the benefit of other family members.
Of course, I realise this may prevent people like Phyllis taking the test in the
first place, so Jane would be no better off, but at least we wouldn’t be in the
difficult dilemma we are in now. Personally, I feel it is wrong to be referring
Jane on for such major surgery when I have information, which I cannot
share with her, that may make this surgery unnecessary. We’ve tried our
 Families and genetic testing: Jane and Phyllis 15

hardest to negotiate with Phyllis and to persuade her of the potential benefit to
unaffected relatives but it seems to fall on deaf ears. I don’t know which side of
the fence I’d come down on if Jane was not contemplating major surgery, if she
just wanted to know in order to be more certain of her risks, but I feel the
potential surgery shifts the balance. I think Jane should be told about Phyllis’s
result, and Phyllis about the disclosure, in as sensitive a way possible.

Author’s comment

While this case is a composite of many different cases, I hope it serves to

highlight the sort of dilemmas that are faced by professionals looking after
both families and individuals. The discussion is centred around breast cancer
and ways of detecting or preventing it. Jane is potentially also at risk of
ovarian cancer. The lifetime risks for this cancer in someone who has
inherited a BRCA1 mutation is up to 60%. Screening is of unproven benefit
although research studies on this are ongoing. Because of the lack of effective
screening for ovarian cancer, some women consider prophylactic removal of
the ovaries to be the right course to take, and this may well be an attractive
option for Jane as she has already completed her family. Although not such a
major operation as a mastectomy, at Jane’s age she might need a period of
hormone-replacement therapy to prevent osteoporosis. Again, her options
would be much clearer if a predictive test were possible for her. This additional
risk of ovarian cancer adds yet further complexities to the case: what role
should requests for additional major surgery such as bilateral oophorectomy
play in weighing up whether to disclose or not? If Jane were not contemplating
any surgery but wanted to continue with screening instead would that make a
difference to whether Phyllis’s result should be disclosed? In this case, Jane
might still be availing herself of unevaluated and expensive screening for many
years that could be shown to be unnecessary if Phyllis’s result was disclosed.
A criticism of the particular case I have chosen might be that it presents a
dilemma only because of the technicalities of a genetic test in its infancy.
Once genetic testing is more advanced, testing of an individual will be less
dependent on initial testing of another relative. This of course may turn out
to be true, but testing for other conditions may become available and also
have to go through the same uncertain stages. Moreover, even when routine
testing of everyone’s entire genome is possible there will be many other
possible scenarios in which information on one person, if not disclosed to a
relative, may prevent that relative knowing their risk. These include the
following scenarios:
A woman with a young disabled son finds out that his problems are due to muscular
dystrophy. She is a carrier of the condition. Her sister has a 50% chance, therefore, that
16 Anneke Lucassen

she is also a carrier and has just revealed she is 10 weeks pregnant but concerned about
bringing a disabled child into the world. The woman refuses to tell her sister of the risk
as she thinks she may terminate a pregnancy. She herself is opposed to termination.
Routine testing for muscular dystrophy would not be available in pregnancy unless a
specific familial mutation were known. (Parker and Lucassen 2004)

A man with a family history of Huntington’s disease (HD) who has tested positive,
marries a woman who wants to start a family. He does not tell her of his diagnosis as he
is worried that she will leave him. (Lucassen and Parker 2004)

Many other conditions exist where confirmation of what the actual condition in
an affected relative is, is of importance for the accuracy of the test in their
relatives, e.g. family history of suspected HD again, in which there may be a
need to confirm that the dementing illness in the relative is in fact HD, rather
than another dementing illness, before a predictive test is accurate.
It might also be suggested, as a criticism of the case, that, had the time
sequence of this case been different the dilemma might have disappeared.
Had Phyllis been referred to clinical genetics before genetic testing had been
carried out, for example, consent could have been asked of her at this point to
disclose any result to her relatives if it were likely to prove helpful to them.
This could even have been made a precondition to testing. Some genetic
departments are now doing this as part of their consent process but it is not
known how many people are thereby deterred from testing altogether, or
indeed how many would refuse to accept the conditions to consent. If people
are deterred, then clearly Jane’s position is no better than in the case as
described (because the test would not have been carried out), but at least
then the clinicians would not be faced with the dilemma of knowing informa-
tion that could help Jane but not be able to disclose it. The placing of
conditions such as these on patients’ access to genetic testing raises a number
of important ethical issues in its own right of course. Could it ever be ethical
to deny a patient access to a test unless he or she were willing to consent to the
use of its results for family members?
The case might also have been different if Jane were referred after the team
already knew of Phyllis’s existence and both of her relationship with Jane and
her wish for non-disclosure. Under these circumstances, it might have been
possible to fudge the issue in discussion with Jane. If the geneticist hadn’t
explained the current limitations of testing so thoroughly it would have been
possible simply to test Jane for Phyllis’s mutation without anyone knowing
and then give her a result. Even so, this would not, of course, constitute
informed consent and fudging of this type could easily come to light at a later
stage leaving professional probity open to question.
This is an area that requires much greater public and professional discus-
sion and debate and I hope that the chapters in this book will contribute to
and enlighten such debate.
 Families and genetic testing: Jane and Phyllis 17

NOTE
1 For more information about inherited breast cancer and genetic testing see also
patient information leaflet in Appendix II.

REFERENCES
Lucassen, A. and Parker, M. (2004). Confidentiality and ‘serious harm’ in genetics:
preserving the confidentiality of one patient and preventing harms to relatives.
Eur J Human Gen, 12(2), 93–7.
Parker, M. and Lucassen, A. (2004). Genetic information: a joint account? BMJ, 329,
165–7.
APPENDIX I Family diagram

brca 45

AGNES STAN brca 46 ovca 57

brca 38 ? Alive
ovca 55 address
not known

EDITH GEORGE
PHYLLIS
Left brca 36
brca 50
Right brca 43
died 44

36
JANE

Female Ovarian cancer

Male Breast cancer

7 9
Deceased male
APPENDIX II Patient information leaflet

This leaflet has been produced by Anneke Lucassen for the Wessex Clinical
Genetics Service, Southampton, UK.
20 Appendix II

Women with
Women with inherited
breast cancer breast cancer

This booklet has been written for people who have a family history of breast
and/or ovarian cancer which could be explained by an inherited factor. It
aims to answer some of the questions you may have.

Is breast cancer inherited?

Usually not. In only about 5 to 10 of every hundred women with breast cancer
is the cancer thought to be due to a strong inherited factor. This factor is an
alteration (called a mutation) in a gene inherited from a parent. Two genes
have been identified that cause a large increase in the risk of developing breast
cancer when they are altered. They are called BRCA1 and BRCA2 (Breast
cancer gene 1 and 2).

What is BRCA1 and BRCA2?

BRCA1 and 2 are genes that everybody has which make a protein that is
important for the normal function of cells. A mutation in these genes alters
the message the genes send to the body, which increases the chances of
developing breast and/or ovarian cancer.

How are BRCA genes inherited?

We all have two copies of each of our genes; one we get from our mother, the
other from our father. When we have children we randomly pass on just one
of each of our pairs of genes. If a person has a mutation in one of a pair of
genes, each of his or her children has a 50:50 chance of inheriting it or not.
The mutation can be inherited from either parent, although the chances of a
man developing breast cancer are much lower than for a woman.
 Patient information leaflet 21

Mutated
gene

Normal
gene

Possible
pregnancies

This shows a mother with a faulty gene but it could be either partner
For every child there is a 50%, or 1 in 2, chance of inheriting the mutation

If a person has not inherited BRCA mutation then they cannot

pass it on to their children.

How do I know if the cancer in my family is due to a mutation in a

BRCA gene?
If you have several closely related family members (such as sisters, mother,
grandmother, aunts who are blood relatives) with breast and/or ovarian cancer,
and if their cancers occurred at a young age (usually below the age of 50), there
may be a breast cancer (BRCA) gene mutation in your family. Remember that
even if this is the case, you may not have inherited it (see above).

Can I have a test to see if the breast cancer in my family is due to a

mutation in a BRCA gene?
This may be possible. A person’s genes can be examined from a blood sample.
However, because only a small proportion of people with breast cancer will
have a BRCA mutation, and the test is technically difficult and takes a long
time, it is at present only offered to people with a very strong family history of
breast/ovarian cancer at a young age. Without this sort of family story, the
test is unlikely to show any mutations.
22 Appendix II

I have got a very strong family history, how do I go about testing?

We need to start by obtaining a sample of blood from a relative in your family
who has had breast or ovarian cancer and look for a mutation. Different
families with breast/ovarian cancer have different mutations in the BRCA1 or
2 genes or even other genes that have yet to be discovered. We need to find
which, if any, is the mutation for your family. Genetic testing is currently
technically difficult and therefore a lengthy process. We know that at present
we cannot find all the different mutations. Our techniques are constantly
improving and in years to come testing will be more straightforward but at
present there will be many families who have a gene mutation that the
laboratory cannot yet find.

What if a relative with breast or ovarian cancer is not available?

Can I be tested even if I have never had cancer?
The test is very difficult to interpret without knowing if a mutation exists in
the family and which one it is. One of the reasons for this is that if we test a
person who has not had cancer and the test does not find a mutation, we
cannot tell whether that is good news (and you have not inherited the
mutation), or whether the test has not been able to find a mutation that is
in fact present (because of the current technical limitations of the test).

Testing you without knowing the mutation for your family would mean we
could not reassure you that you had not inherited the cancer tendency. In
reality in a family with one of the BRCA1 or 2 mutations which cause cancer,
there is always a 50% (1 in 2) chance of this (see diagram).

So testing is a two-stage process?

Yes. The first step, the ‘‘diagnostic test’’ looks for the mutation in an affected
relative. If we cannot find it, then at present testing is not possible in you. We
would hope that testing will improve and that a mutation will be found in the
future.

If we do find the mutation in an affected relative then we can examine your

blood to see whether or not you have the same mutation. This is called a
‘‘predictive test’’. This second test is very accurate and takes just a few weeks.
There is a 50% chance it will be positive (you have inherited) and a 50%
chance it will be negative (you have not inherited the gene mutation). A
predictive test in the presence of a known mutation in a family member is
highly accurate.
 Patient information leaflet 23

Does everyone who inherits a mutation in a BRCA gene get breast

or ovarian cancer?
No. The risk of developing these cancers is high, but not 100%. We do not yet
know why some women with the mutation develop cancer and some do not.
Lifestyle or other genetic factors may play a role.

Remember that the risk of developing cancer is not the same as the risk of
dying from cancer. Even if cancer develops, there is a chance that the disease
can be cured if detected and treated early.

How high is my risk of cancer if I have inherited a BRCA mutation?

The risk of developing breast cancer in your lifetime may be as high as 80%
and as high as 60% for ovarian cancer. That is, up to 8 out of every 10 women
with the BRCA mutation will develop breast cancer at some point in their
lives; up to 6 out of every 10 women with the mutation will develop ovarian
cancer. The exact risk varies depending on where in the gene the mutation lies
and on possibly other genetic and lifestyle factors.

If I have not inherited a BRCA mutation can I still get cancer?

Unfortunately, yes. Although the risk is then no higher than for anyone else in
the general population, there is still a chance of developing cancer, because
cancer can occur for other reasons. Every woman has a roughly 10% (1 in 10)
chance of developing breast cancer in their lifetime, so even with a negative gene
test, there is still a chance of developing breast cancer. However, this cancer is
more likely to develop at a later age than a cancer due to a BRCA gene mutation.

What happens if a man has a mutation in a BRCA gene?

Men do not have as high a risk of developing breast cancer as women do, but
they can get breast cancer. There may also be a slightly increased risk of
developing prostate cancer. The exact increase in risk is not yet known.
Research studies are looking at this.

Men can pass on the mutation to their sons and daughters.

Are BRCA1/2 the only genes that can cause hereditary breast cancer?
No. Probably about three-quarters of all inherited breast cancer is due to
mutations in BRCA1 or BRCA2. There are likely to be other genes that
increase the risk of developing breast cancer which have not yet been found.
24 Appendix II

If I have a BRCA mutation when will I develop cancer?

You may never develop cancer at all. It is not possible to predict whether you
will or will not develop cancer or at what age you will develop it.

What can be done about the risk of developing breast or ovarian

cancer?
* Some women will want to be followed closely by their doctor to detect

cancer as early as possible, since treatment is more effective in the early

stages. This may include regular breast examinations and mammograms.
Unfortunately these tests will not be able to pick up all cancers. In general,
mammograms are more able to pick up cancers in older women. In younger
women the doctors need to plan carefully how often mammograms are
done because they carry a greater risk. The benefits of mammography are
not entirely clear in younger women.
* Some women might consider preventative or prophylactic surgery

(removing the breasts or ovaries before cancer occurs). This does not
completely eliminate the chance of cancer but will reduce it by a large
amount. Other leaflets describe this in more detail.
* There are studies underway on different types of drugs that may decrease

the risk of developing these cancers.

These can all be discussed in more detail at the clinic.

What is the advantage of predictive BRCA testing?

Women who have a mutation in a BRCA gene are at high risk of developing
breast and ovarian cancer. Knowing your risks may help you with decisions
about your life and may allow you to take action to reduce your risks. You can
talk to your doctor about the screening and other options available to you.
However, it is important to know that at present there is no method of
detection or prevention that has been proven to be completely effective.
Despite this, some women would rather know whether they have inherited
a BRCA mutation than live with the uncertainty.

Remember there is a 50% chance that the test will show you have not
inherited the mutation. This means you cannot have passed it on to any of
your children or future children. You will also not need any screening until
you start the population screening at 50 years.

Remember ‘‘predictive’’ means a test on a person who has not had cancer but who
is closely related to someone who has and in whom a mutation has been found.
 Patient information leaflet 25

What are the risks of BRCA testing?

If a mutation is found that increases your risk of developing cancer it may
affect your ability to get insurance (e.g. health, life, disability). Currently the
insurance industry has agreed it will not ask about genetic testing for the
majority of policies, but this position may change in the future.

You may want to review your insurance before testing. You should talk to
your doctor about how the information will be kept in your medical records.

Some people experience many emotions when they are told they have a gene
that increases their risk of cancer. Anger, shock, anxiety, worry about their
health, worry or guilt about possibly passing the gene on to children are all
normal reactions. Some people may also feel guilty if they do not carry the
change in the gene when other close family members do so.

Remember that we can tell you your risk is increased but we cannot tell you
for certain when or even if you will develop cancer.

Genetic testing in a family can affect other family members, they may need
to be told that they too are at increased risk or unexpected information may
be revealed, for example, someone may disclose that a family member
is adopted. Therefore, genetic testing may sometimes affect relationships
within families.

Is there an alternative to genetic testing?

You may choose not to have genetic testing. Whether or not you are tested,
you should talk to your doctor about starting a programme to detect cancer
early.

I’ve heard of research studies involving people with a family

history of cancer. How can I find out more?
There are currently several different national and international research
studies. More information can be obtained from the address overleaf. It is
important to remember that research studies may not benefit you directly,
but may help others or future generations.

Talk to your doctor about all of the options before deciding on a plan of
action that is best for you.
26 Appendix II