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Health Policy Advisory Committee on
Technology
Technology Brief
BreastNext™: a 14-gene sequencing panel for the diagnosis
of hereditary breast/ovarian cancer
May 2013
© State of Queensland (Queensland Health) 2013
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Technology, Company and Licensing
Register ID
WP152
Technology name
BreastNext™: gene sequencing panel for the diagnosis of
hereditary breast/ovarian cancer
Patient indication
For use in women with a genetic predisposition to breast
and/or ovarian cancer who have tested negative to BRCA1
and BRCA2
Description of the technology
BreastNext™ is a 14-gene sequencing panel intended for use in individuals who are
considered to have a genetic predisposition to developing breast cancer due despite testing
negative to BRCA1 and BRCA2. Individuals would be considered to be at an increased risk of
breast cancer if they have a diagnosis of multiple primary breast cancers or bilateral cancer
or male breast cancer, a diagnosis of breast cancer at a young age (<50 years), and/or three
or more close relatives with a diagnosis of breast cancer. The test uses next-generation
sequencing to detect the presence of mutations in the 14 genes listed in Table 1, which may
indicate an increased risk of breast cancer. The breast cancer risk of mutations associated
with the genes in the BreastNext™ panel is described in Figure 1. Ambry Genetics
Corporation provide two other panels, OvaNext™ and CancerNext™, that test for mutations
in the same genes as BreastNext™, in addition to several other genes.1 Many of the genes
included in BreastNext™ are not just associated with breast cancer (Table 1) and therefore a
mutation in one of these genes may indicate an elevated risk of a number of different
cancers, making a specific management and surveillance strategy difficult.
Figure 1
Breast cancer risk versus the mutation frequency of the genes in the general
2
population (composition not stated)
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
1
Table 1
Genes
Genes included in various hereditary cancer panels provided by Ambry Genetics
Cancer site associated
ATM
Ovaries, breast, pancreas
BARD1
Ovaries, breast
BRIP1
Ovaries, breast
CDH1
Breast, gastric, colorectal
CHEK2
Ovaries, breast, colorectal,
uterine
Ovaries, breast
MRE11A
MUTYH
NBN
Breast, duodenum,
colorectal
Ovaries, breast
PALB2
Ovaries, breast, pancreas
PTEN
Breast, thyroid, endometrial,
colorectal, kidney
RAD50
Ovaries, breast
RAD51C
Ovaries, breast
STK11
Ovaries, breast, pancreas,
duodenum, colorectal
Tp53
Breast, colorectal, brain
BreastNext
OvaNext
CancerNext
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
MLH1
MSH2
MSH6
Ovaries, endometrial,
colorectal, urinary tract,
stomach, hepatobiliary tract
EPCAM
PMS2
APC
BMPR1A
SMAD4
1, 3
Stage of development in Australia
Yet to emerge
Established
Experimental
Established but changed indication or
modification of technique
Should be taken out of use
Investigational
Nearly established
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
2
Australian Therapeutic Goods Administration approval
Yes
ARTG number (s)
No
Not applicable
Licensing, reimbursement and other approval
BreastNext™ is not listed on the ARTG. As of 1 July 2010, the new TGA regulatory framework
requires all new in vitro diagnostic medical devices (IVDs) to be listed on the Australian
Register of Therapeutic Goods (ARTG). IVDs encompass pathology tests. BreastNext™ would
be classified as a Class III IVD and as such be required to be registered on the ARTG,
however IVDs developed “in-house” are only required to have approval and yearly
validation from NATA1. Australian companies that collect samples to be sent to overseas
companies for analysis do not have to be listed on the ARTG, however all equipment used to
collect and transport samples need be registered (personal communication TGA).
BreastNext™, as a laboratory-developed test, is not required to have Food and Drug
Administration approval. In the United States, genetic testing may be conducted by clinical
laboratories that are licensed and accredited under the US Clinical laboratory Improvement
Act (CLIA approval) 4
Technology type
Diagnostic
Technology use
Diagnostic
Patient Indication and Setting
Disease description and associated mortality and morbidity
Breast cancer occurs when abnormal cells grow and multiply out of control. Breast tissue
consists mainly of fat, glandular tissue (arranged in lobes), ducts and connective tissue
(Figure 2). Breast cancer originates in the ducts of the breast or in the lobules. The most
common histological type of breast cancer is invasive ductal carcinoma (70-80%). There are
two types of non-invasive breast cancer: ductal (DCIS) and lobular (LCIS) in-situ carcinoma,
which are confined within the terminal duct lobular unit and the adjacent ducts but have
not invaded through the basement membrane. LCIS is usually not identified via a
mammogram but is an incidental finding during biopsy. DCIS is usually diagnosed due to
micro-calcifications appearing on mammograms. Invasive breast cancer poses the risk of
having given rise to distant metastases that at some later time will threaten a woman’s life. 5
1
National Association of Testing Authorities, Australia
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
3
Figure 2
Anatomy of the breast
Number of patients
In Australia during 2008, the most commonly diagnosed cancer in females was breast
cancer, with 13,567 cases at an age-standardised incidence rate (ASR) of new breast cancer
cases 115 per 100,000. In addition, the leading cause of burden of disease from cancer in
females during 2008 was breast cancer, representing a total of 28 per cent of the total
cancer burden and four per cent of the total burden of disease in Australia, accounting for
61,300 DALYs.2 The majority of cases (69%) were diagnosed in women aged 40-69 years. The
overall risk of being diagnosed with breast cancer in 2008 for a female before the age of 85
was one in eight, with a mean age at first diagnosis of approximately 60 years. In 2007,
breast cancer was the second most common cancer causing death in Australian females,
accounting for 2,680 deaths with an ASR of 22.1 per 100,000. On average, one in 37
Australian women will die from breast cancer before the age of 85 years.6
As in Australia, breast cancer was the most commonly diagnosed cancer in females in New
Zealand during 2009, representing 28.4 per cent of all new cancer registrations in females.
In that period the number of new breast cancer cases registered was 93 per 100,000
females, representing 2,759 women diagnosed with the disease. For the same time, breast
cancer was the second most common cause of death, accounting for 16.3 per cent of female
cancer deaths, representing. The number of deaths from breast cancer in the same year was
658 at an ASR of 19.9 per 100,000. Mortality rates are higher in Māori females (27.4)
compared to non- Māori females (19.2).78
It is difficult to estimate the number of women who may be at a genetic predisposition to
breast cancer, however it is thought that gene mutations account for 5-10 per cent of all
2
DALYs = disability affected life years
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
4
breast cancer.9 The mutation frequency rates for three of the most well characterised
genes, BRCA1, BRCA2 and Tp53, are summarised in Table 2. Several of the genes included in
the BreastNext™ panel are involved in DNA repair: CHEK2, ATM, BRIP1 and PALB2. These
genes are associated with an estimated two-fold risk of breast cancer in women and have
been shown by numerous studies to be rare in the population.10 Mutations in the PALB2
gene were identified in 10/923 (1.0%) individuals with familial breast cancer compared with
0/1,084 controls.11 Mutations in the CHEK2 gene occur with a frequency of approximately
one per cent in healthy individuals but is present in 5.1 per cent of individuals with breast
cancer from 718 families that do not carry mutations in BRCA1 or BRCA2. 12 Seal et al (2006)
identified mutations in the BRIP1 gene in 9/1,212 (0.7%) individuals with breast cancer from
BRCA1/BRCA2 mutation-negative families but in only 2/2,081 (0.1%) controls.13 Inherited
mutations in the BRIP1 and PALB2 genes are associated with a 20-50 per cent lifetime risk of
breast cancer.14
Mutations in the PALB2 gene are rare in Australian women but when present are associated
with a high estimated risk of breast cancer (91%; 95% CI [44, 100]) to age 70 years.
Screening for PALB2 in 871 unrelated individuals from high-risk breast and/or ovarian cancer
families enrolled in the Familial Cancer Centre in Australia, identified eight women with the
mutation, a rate of 0.92 per cent.15 Dite et al (2010) characterised the risk of developing
cancer in relatives of women with early on-set breast cancer (<35 years).16 Of the 504 young
women with breast cancer, only 41 carried a known BRCA 1 or BRCA2 mutation. Cancerspecific standardised incidence ratios (SIRs) were estimated for the 2,208 first-degree
relatives of the women, by comparing the number of affected relatives with that expected.
For relatives of carriers, the female breast cancer SIRs were 13.13 and 12.52 for BRCA1 and
BRCA2, respectively. The ovarian cancer SIR was 12.38 for BRCA1 and the prostate cancer
SIR was 18.55 for BRCA2. Relatives of the non-carriers had SIRs for female breast, prostate,
lung, brain and urinary cancers of 4.03, 5.25, 7.73, 5.19 and 4.35, respectively. These results
indicate that first-degree relatives of women with very early-onset breast cancer are at
increased risk of cancers that is not explained by mutations in the BRCA1 and BRCA2 genes.
Many studies have been published describing other possible causative genes that may be
associated with breast cancer.10
Causative mutations may not be identified, however this does not exclude the possibility of
a genetic predisposition. First-degree relatives who failed to have a mutation identified
would still be considered to be at a 50 per cent risk of having an inherited mutation and
would enter a surveillance programme, which may include screening by annual
mammogram or MRI.17
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
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Table 2
Mutation frequency for genes associated with a genetic predisposition to cancer
Mutation
frequency
Gene
Major sites at risk
Risk of cancer at
age 75 years
where a family
specific mutation
has been
identified
BreastOvaries
40-80%
10-60%
Prostate
Other sites with
up to a 10%
lifetime risk
BRCA1
1:1,000
BRCA2
1:1,000
BreastOvaries
40-80%
10-40%
Male breast,
prostate, pancreas
1:10,000
Breast bone
Soft tissue
50%
<10-50%
Brain, lung,
adrenal gland
p53
Speciality
Women’ health, cancer
Technology setting
Specialist hospital
17
Impact
Alternative and/or complementary technology
Additive or complementary technology: New technology is used alongside the current
technology, in combination with but not replacing them.
Current technology
Cancer Australia has developed on on-line tool (FRA-BOC) to be used by health professionals
for the assessment of a patient’s risk of developing breast or ovarian cancer based on family
history and other factors.18 Referral to a family cancer clinic for possible genetic is
appropriate if the patient has:
been assessed as being at potentially high-risk of developing breast or ovarian cancer
(Category 3 based on FRA-BOC assessment);
family with an unusual pattern of early onset cancer i.e. breast or ovarian cancer
occurring at a young age;
multiple relatives affected by breast cancer (male or female) or invasive epithelial
ovarian cancer;
at least one relative affected by both breast cancer and invasive epithelial ovarian
cancer;
relatives affected with bilateral breast cancer, especially at a younger age (<50); or
a personal or family history of breast or ovarian cancer and indicates that she is of
Jewish descent.
The BRCA1 and BRCA2 genes were discovered in 1994 and 1995, respectively. Both genes
are tumour suppressors required for DNA repair and other cellular functions that are
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
6
important in the maintenance of genetic integrity. Mutations in either of these genes may
result in DNA repair via error-prone repair mechanisms, leading to an accumulation of
mutations and rearrangements.19 Mutations in these genes are inherited as autosomal
dominant, meaning that each child has a 50 per cent chance of inheriting the mutation from
either the mother or the father.17 Although rare (less than 1% of all BRCA mutations), it is
possible for someone to have mutations in both BRCA1 and BRCA2 genes. These individuals
do not have a higher risk of cancer nor more severe disease compared to single mutation
carriers.20 Individuals considered to have a genetic predisposition to breast or ovarian
cancer may be advised to undergo BRCA1 and BRCA2.
In Australia, BRCA1 and 2 testing is not listed on the Medicare Benefits Schedule but can be
accessed through publically funded Family Cancer Clinics. Most testing is conducted at no
cost to the consumer, however this may vary from state-to-state. General practitioners may
refer individuals to specialists in familial cancer or clinical geneticists, where appropriate
counselling may be provided before and after BRCA1 and BRCA2 testing. Myriad Genetics
Inc hold the patents for BRCA1 and BRCA2 and Genetic Technologies Ltd holds the exclusive
Australian licence for the tests. However, in 2003 and again in 2008, Genetic Technologies
Ltd decided not to enforce its licence and testing can be carried out by all Australian
specialist genetic laboratories.9 There are approximately 10 laboratories in Australia which
currently provide this service at an estimated cost of $1,650 (personal communication
Westmead Familial Cancer Service). Testing for BRCA1 and 2 involves the extraction of DNA
from a patient's blood sample and each exon of each gene is amplified by polymerase chain
reaction, which is followed by bidirectional sequencing.20 Results may take several weeks to
be made available.
Diffusion of technology in Australia
There is little diffusion of this technology in Australia. The Peter MacCallum Cancer Centre is
aware of at least one Australian patient who recently had a sample sent to Ambry Genetics
to be analysed by the BreastNext™ panel at a full cost to herself. There appears to be a
reluctance by Australian clinicians to use this technology due to potential difficulties in
interpreting the significance of mutations in some of the genes included in the panel
(personal communication Peter MacCallum Cancer Centre). Australian patients seeking to
undergo testing with BreastNext™ would require a clinician to order the test.
International utilisation
Country
Level of Use
Trials underway or
completed
United States
Limited use
Widely diffused

BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
7
Cost infrastructure and economic consequences
The current listed price of the BreastNext™ panel is US$4,120, with the OvaNext™ and
CancerNext™ panels costing US$5,310 and $5,830, respectively.21 As previously mentioned,
the cost of testing a patient in Australia for BRCA1 and BRCA2 is approximately $1,650. The
cost of testing an Australian patient with BreastNext™ could not be ascertained. With the
advent of next generation sequencing it is expected that costs will fall making it possible to
sequence multiple genes simultaneously.
Although the company states that clinicians can access genetic counselling services to assist
with test selection, case reviews and result interpretation3, the cost of counselling patients
who have undergone testing with BreastNext™ would likely have to be met by state funded
family cancer clinics. A positive test in any of the genes included in the panel may result in a
surveillance programme that may include annual screening and imaging, which could have a
cost impact on the public health system.
As first-degree relatives would enter a surveillance programme whether they tested positive
or negative for an inherited gene mutation17, testing may be an unnecessary cost.
Ethical, cultural or religious considerations
Patients need to be offered appropriate counselling and sufficient information on the
advantages and disadvantages of screening tests, the likelihood of a false positive or false
negative result and the consequences of a positive result. Mutations detected in some of
the genes included in the BreastNext™ panel may be considered amorphous in that they
represent an increased risk, but there is little that may be done about that risk. In addition,
the risk is not specific to one cancer, for example, a mutation in the Tp53 gene may
represent an increased risk of cancer of the breast, colorectum or brain, making surveillance
difficult. A positive test may therefore result in undue worry and stress on the patient.
Interestingly though, a US review of screening for inherited breast or ovarian cancer
reported decreased rather than increased breast cancer worry or anxiety after risk
assessment and testing, though studies with depression as an outcome had mixed results.22
Gene panel testing such as this are currently only accessible on a user-pays basis, which
raises issues of equity in that only those women who can afford to pay in excess of $4,000
can access this additional information.
Evidence and Policy
Safety and effectiveness
No peer reviewed studies could be identified in the literature that describes the use of the
BreastNext™ panel in women considered to have a predisposition to breast cancer. Ambry
Genetics have a number of conference proceedings published on their website, which will
be summarised here. All of these presentations cite the paper by Walsh et al (2010), who
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
8
described the use of massively parallel sequencing for the detection of multiple inherited
mutations.14
Walsh et al (2010) targeted a panel of 21 genes associated with inherited breast and ovarian
cancer. Oligonucleotides were designed to cover coding regions, non-coding intronic
sequences and 10-kb3 genomic sequence flanking each gene. All genes apart from BRCA1,
BRCA 2 and PSM1 are included in either the BreastNext™ or OvaNext™ panels. Target DNA
was isolated from blood of 20 women with a known inherited mutation previously identified
via Sanger sequencing (level III-1 diagnostic evidence). Researchers were blinded to the
subject’s mutational status and candidate variants were confirmed by conventional Sanger
sequencing. DNA libraries were prepared and enriched before hybridisation to the custom
made oligonucleotides followed by sequencing. Average coverage was 1,286 reads per
nucleotide. The resulting DNA sequences were aligned to the human reference genome and
to be considered a possible variant the mutation had to be present on both the sequenced
DNA strands and represent ≥15 per cent of total reads. Potential variants are summarised in
(Table 3) and include point mutations, small insertions and deletions. A number of
additional variants were identified in BRCA1 and BRCA2 (not included in table). 14
Table 3
Point mutations, insertions and deletions identified by Walsh et al
Gene
Mutation type
Mutation size
(bp)
% variant
BRIP1
Deletion
1
43
CDH1
Nonsense
1
46
Deletion
1
15
MLH1
Slice
1
40
MSH2
Nonsense
1
49
p53
Missense
1
41
PALB2
Deletion
2
49
STK11
Slice
1
44
CHEK2
Walsh et al (2011) conducted a follow-up study using the same 21-gene panel in 360
consecutive women who were undergoing surgery for carcinomas of the ovaries (n=273),
peritoneal (n=48), fallopian tubes (n=31) and synchronous endometrial and ovarian
carcinomas (n=8).23 Women were not selected for family history, however 157 women
reported a family history of breast or ovarian cancer and 97 a history of colon, uterine or
pancreatic cancer. DNA was sequenced as described above and candidate variants were
confirmed by Sanger sequencing level III-2 diagnostic evidence). A total of 85 loss of
function mutations were identified in 82/360 (22.8%) women, with three women having
3
Kb= kilo bases
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
9
two mutations. Mutations were identified in 12 of the 21 genes (Figure 3). In discussion, the
authors state that reagent costs of the 21 gene panel (the BROCA test) are approximately
$200 and that the test is not patented.
Figure 3
Mutations were detected in 12 of the 21 genes in 82 women
A similar study by Kuusisto et al (2011) screened 82 high-risk Finnish women who were
BRCA1 and BRCA2 founder-mutation4 negative for seven breast cancer susceptibility genes:
BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50 and CDH1. Of these women, 57 had breast
cancer, eight had bilateral breast cancer, one had ovarian cancer, five had both breast and
ovarian cancer and 11 were unaffected. Sequenced DNA from these subjects was compared
to sequenced DNA from 384 healthy female volunteers (not all of whom were screened for
all mutations). Mutation screening was performed by direct sequencing. Three previously
described mutations in BRCA1 and CHEK2 were identified in 11/82 (13.4%) high-risk women.
Fourteen novel mutations were found: three in BRCA2, BRIP1 and PALB2, and five in CHEK2.
Sixteen different BRCA1 and BRCA2 variants were identified with all but two BRCA1 having
previously been reported to be neutral. One of these two variants was observed in 4/82
(4.9%) of the high-risk women and in 6/367 (1.6%) of the controls. The remaining BRCA1
variant (a deletion) was found in only one woman, with later analysis identifying two family
members with the same deletion. Two previously reported CHEK2 mutations were identified
in 10/82 (12.2%) of the high-risk women. One woman had both of these mutations and two
also had missense mutations in the PALB2 gene. Although the authors felt that it was
important to provide information to assist counselling and surveillance to BRCA1 and BRCA2
negative patients and their families to in regard to potential mutations, this study
4
Founder mutation: a mutation that appears in the DNA of one or more individuals who are founders of a
distinct population, and are passed down to other generations.
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
10
emphasises the number of potential mutations that may have to be screened for in any
given high-risk population.24
The results of the first 400 BRCA1 and BRCA2-negative women to receive testing with
BreastNext™ were reported to the 2013 conference of the US National Consortium of Breast
Centers (NCBC). The NCBC is an “organisation of breast professionals, breast centres,
providers of service to care providers, and corporations that supply equipment and
pharmaceuticals to care providers.” Of the 400 women, 41 (10%) were found to have a
mutation in the following genes: PALB2 (n=9), ATM (n=9), CHEK2 (n=8), MUTYH (n=4),
BARD1 (n=3), RAD50 (n=3) and one each in pTEN, RAD51C, Tp53, MRE11A and NBN (level IV
diagnostic evidence).25 However, the significance of these results and the implications for
patients of these positive results were not discussed. Positive tests may be difficult to
interpret if the genetic variant is not the known founder mutation. 26 In addition, mutations
may occur in genes of known importance, but whether these mutations result in functional
changes resulting in consequences for the health of the individual may remain unknown.
Economic evaluation
No economic evaluation could be identified. Walsh et al (2010) discussed the potential costsavings when conducting multiple analyses across a number of mutations. A price of
US$3,340 was quoted for comprehensive BRCA1 and BRCA2 testing, and that if negative,
additional mutations could be tested for individually at a cost of $650. He then goes on to
quote an approximate cost for the analysis of one sample by the 21-gene panel described in
his study as $1,500. As it is unlikely one sample would be run during this analysis, economies
of scale would reduce this cost substantially.14
Ongoing research
No on-going clinical trials of the BreastNext™ panel were identified.
Other issues
No issues were identified.
Summary of findings
The 21-gene and 14-gene panels detected a number of mutations in candidate genes, which
may be of significance in women considered to be at a genetic predisposition to breast or
ovarian cancer. The impact of these findings on patient outcomes was not discussed in any
of the included papers. It may be assumed that these women and their first-degree relatives
would then enter a surveillance programme. In Australia, first-degree relatives would be
eligible to enter into such a programme even if testing for BRCA1 and BRCA2 was negative,
therefore it is difficult to gauge the usefulness of tests such as BreastNext™ and OvaNext™.
BreastNext™: gene panel for the diagnosis of hereditary breast/ovarian cancer: May 2013
11
Of concern, however, is that these tests may be accessed by women who may not require
testing, and that this may have consequences for the public health system.
HealthPACT assessment
Although some of the genes included in the BreastNext™ panel may be associated with
breast cancer, there is a paucity of evidence linking all of the included mutations with the
disease. There were no peer-reviewed studies identified that could demonstrate the clinical
utility of this product and therefore the impact this product may have on clinical decision
making cannot be determined. Of concern is that these tests may be accessed by women
who may not require testing, and that this may have consequences for the public health
system. Therefore it is recommended that no further research on behalf of HealthPACT is
warranted at this time.
Number of studies included
All evidence included for assessment in this Technology Brief has been assessed according
to the revised NHMRC levels of evidence. A document summarising these levels may be
accessed via the HealthPACT web site.
Total number of studies
Total number of Level III-1 diagnostic evidence studies
Total number of Level III-2 diagnostic evidence studies
Total number of Level IV diagnostic evidence studies
4
1
1
2
References
1.
Ambry Genetics (2013). Hereditary cancer panels Available from:
http://www.ambrygen.com/hereditary-cancer-panels [Accessed 15th April 2013].
2.
Ambry Genetics (2013). Patient information: Genetic Testing for Hereditary Breast
Cancer. Available from:
http://www.ambrygen.com/sites/default/files/BreastNext_Patient_Interactive.pdf
[Accessed 16th April 2013].
3.
Ambry Genetics (2013). Hereditary Cancer Testing: BreastNextTM. Available from:
http://www.ambrygen.com/sites/default/files/BreastNext_Diagnostic_Interactive.pdf
[Accessed 16th April 2013].
4.
Ambry Genetics (2012). The Case for Clinical Adoption of Hereditary Breast Cancer
Panel Testing. Available from:
http://www.ambrygen.com/sites/default/files/BreastNext_WhitePaper_112812_0.pdf
[Accessed 12th April 2013].
5.
Avril, N.&Adler, L. P. (2007). 'F-18 Fluorodeoxyglucose-Positron Emission Tomography
Imaging for Primary Breast Cancer and Loco-Regional Staging'. Radiologic Clinics of
North America, 45 (4), 645-57.
6.
AIHW & CA (2012). Breast cancer in Australia: an overview, Australian Institute of
Health and Welfare & Cancer Australia, Canberra
http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=10737423006.
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7.
Ministry of Health (2012). Cancer: New registrations and deaths 2009, New Zealand
Ministry of Health, Wellington http://www.health.govt.nz/publication/cancer-newregistrations-and-deaths-2009.
8.
Ministry of Health (2010). Cancer: New Registrations and Deaths 2007, New Zealand
Ministry of Health, Wellington http://www.moh.govt.nz/moh.nsf/indexmh/cancerreg-deaths-2007-jun10.
9.
BCNA (2011). Genetic testing Background Paper. [Internet]. Breast Cancer Network
Australia. Available from:
http://www.bcna.org.au/sites/default/files/genetic_testing_background_paper.pdf
[Accessed 15th April 2013].
10.
Easton, D. F., Pooley, K. A.et al (2007). 'Genome-wide association study identifies
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Search criteria to be used (MeSH terms)
Genetic Predisposition to Disease
Germ-Line Mutation
Genetic testing
Risk Assessment
Breast Neoplasms/diagnosis/ genetics
Mutation
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