Hereditary Breast/Ovarian Cancer
Prepared by:
June C Carroll MD, CCFP, FCFP
Sydney G. Frankfort Chair in Family Medicine
Mount Sinai Hospital, University of Toronto
Andrea Rideout MS, CGC, CCGC
Certified Genetic Counsellor
Project Manager – The Genetics Education Project
Funded by:
Ontario Women’s Health Council
Version: March 2009
Acknowledgments

Reviewed by:
 Members of The Genetics Education Project

Funded by:
The Ontario Women’s Health Council
as part of its funding to
The Genetics Education Project
* Health care providers must use their own clinical
judgment in addition to the information presented herein.
The authors assume no responsibility or liability resulting
from the use of information in this presentation.
Outline
Sporadic versus familial cancer
 Hereditary breast cancer syndromes
 Referral guidelines
 Benefits, risks and limitations of genetic
testing
 Management
 Cases

Cancer
All cancer involves changes in genes….
Threshold effect:
 During mitosis & DNA replication
 mutations


occur in the cell’s genetic code
Mutations are normally corrected by DNA repair
mechanisms
If repair mechanism or cell cycle regulation
damaged
 Cell
→
→
accumulates too many mutations
reaches ‘threshold’
tumor development
Sporadic Cancer

All cancer arises from changes in genes….
 But

NOT all cancer is inherited
Most breast cancer is sporadic ~ 80%
 Due
to mutations acquired over a person’s
lifetime:
 Cause unknown – multifactorial
 Interaction
of: age environment, lifestyle (obesity,
alcohol), chance, unknown factors

Sporadic cancer generally has a later onset
Clustering of Cancer in Families

11% lifetime risk of developing breast cancer

~20% of women with breast cancer have a family history:

10 -15% of breast cancer is familial:

Due to some factor in the family





Environmental
Undiscovered gene mutation
Chance
Generally not eligible for genetic testing
5-10% of breast cancer is hereditary:

Caused by an inherited gene mutation which causes increased risk
for cancer



Variety of cancer syndromes
About 2/3 of these - BRCA 1 or BRCA 2 mutations
May be eligible for genetic testing
Proportion of Hereditary Breast
Cancer
Familial 10-15%
Hereditary 5-10%
Sporadic 80%
Knudson ‘two-hit’ Model
Sporadic Cancer
ONE HIT
(hit=mutation)
Birth: Two non-mutated
copies of the gene
SECOND
HIT
One mutation in one gene;
Second gene non-mutated
CANCER
Two mutations - one in
each gene
Knudson ‘two-hit’ Model
Hereditary Cancer
ONE HIT
(hit=mutation)
Birth: Two non-mutated
copies of the gene
SECOND
HIT
One mutation in one gene;
Second gene non-mutated
CANCER
Two mutations - one in
each gene
Compared to sporadic cancer,
people with hereditary cancer have…
A
higher risk of developing cancer
A younger age of onset of cancer
Generally
Multiple
< 50 years of age
primary cancers
Hereditary cancer is less common in the
general population than sporadic cancer
Genes involved in hereditary
breast/ovarian cancer

> 2,600 mutations in:
 BRCA1-
chromosome 17
 BRCA2 - chromosome 13


Autosomal dominant transmission
Carrier frequency of BRCA1& 2 mutations
– 1/1,000 in general (Caucasian) population
 1/40 - 1/50 in Ashkenazi Jewish people
 ~1/500


3 common mutations in Ashkenazi Jews
Unique French Canadian mutations
Autosomal Dominant Inheritance
Legend
Normal BRCA genes
BRCA mutation
Bb
bb
Bb
Susceptible
BRCA gene
bb
Population
Risk
Bb
Susceptible
BRCA gene
B: BRCA gene
with mutation
b: normal
BRCA gene
bb
Population
Risk
BRCA1 and BRCA2
What happens when their function
is compromised ?

Both genes are tumor suppressors:
 Regulation
of cell growth
 Maintenance of cell cycle

Mutation leads to:
 Inability
to regulate cell death
 Uncontrolled growth, cancer
Consequences of having a BRCA mutation:
Estimated cancer risk by age 70
Breast Cancer ♀
BRCA Mutation
Carriers
In General
Population
50-85%
11%
40-60%
1-2%
10-20%
1-2%
≤6%
Rare
BRCA1 & BRCA2
Ovarian Cancer
BRCA1
Ovarian Cancer
BRCA2
Breast Cancer ♂
BRCA2
Who should be offered referral for genetic
counselling and/or genetic testing?....

Multiple cases of breast or ovarian cancer on same side
of family, especially






in closely related relatives
in more than one generation
when breast cancer is diagnosed
before age 50
A family member with breast cancer
diagnosed before age 35
A family member with both breast and ovarian cancers
An Ashkenazi Jewish heritage, particularly with relatives
with breast or ovarian cancer
…Who should be offered referral for genetic
counselling and/or genetic testing?





A family member with primary cancer in both breasts
(especially if before age 50)
A family member with ovarian cancer
A family member with male breast cancer
A family member with an identified
BRCA1 or BRCA2 mutation
USPSTF 2005 recommends referral for genetic
counselling and evaluation for BRCA testing to
women with family history indicating increased risk
of BRCA mutations
Case: Rachel
 Rachel
- healthy 40 year old
Concerned
about her risk for cancer
Family history of both breast & ovarian
cancer
Case: Rachel’s family history
LEGEND
Breast cancer
Ov Ca
Died 48
Ovarian cancer
Br Ca
Dx 38
Br Ca
Dx 30
Ov Ca
Dx 40
RACHEL
age 40
Rachel was referred to genetics…
A genetics consultation involves:
Detailed family history information
 Pedigree documentation

 Confirmation
of cancer history: pathology
reports/death certificates
Medical & exposure history
 Empiric risk assessment
 Hereditary cancer / genetic risk
assessment
 Psychosocial assessment

Psychological Aspects to Consider

Motivation for genetic testing:

Reduce uncertainty

Learn about risk for children

Childbearing/marital decisions

Explore further surveillance/treatment options

Perceived risk

Expectations of genetic testing

Psychological well-being – current & past

prior experiences with cancer

prior loss/ disruptions associated with cancer
approaching age of parent’s diagnosis or
death from cancer

A genetics consultation involves:

Assessment of eligibility for genetic testing
risk of a mutation must be ≥10%
for most provincial programs
 Most appropriate family member to test first
 Estimated


Discussion of risks, benefits & limitations of test
Testing and disclosure of genetic test results
 Will


be months before results are available
Discussion of types of results and what they
mean
Screening/management recommendations
Genetic Testing





Available at regional genetic centres and familial cancer
clinics
Covered by provincial insurance plans (i.e. OHIP) if
criteria are met:
Ontario
US Privative Lab
Full gene testing
$1,400CDN
$3,120 USD
Ashkenazi Panel
$350
$535
Familial mutation
$250
$440 February 2009
Testing is only offered if the risk of mutation is ≥10%
Test highest risk affected individual first
Only in exceptional circumstances will testing be offered
to unaffected individuals
Results from Genetic Testing

Positive
 Deleterious

mutation identified
Negative
 Interpretation
differs if a mutation has previously been
identified in the family
 Mutation known – true negative
 Mutation unknown – uninformative

Variant of unknown significance
 Significance
will depend on how variant tracks
through family - i.e. is variant present in people with
disease?
 Can use software to predict functional significance
 Check with lab to see if reported previously
Risks/Benefits/Limitations
of genetic testing
Positive test result
Potential Benefits:




Clinical intervention may
improve outcome
Family members at risk
can be identified
Positive health behaviour
can be reinforced
Reduction of uncertainty
Potential Risks:






Adverse psychological
reaction
Family issues/distress
Uncertainty -incomplete
penetrance
Insurance/job discrimination
Confidentiality issues
Intervention carries risk
Risks/Benefits/Limitations
of genetic testing?
Negative test result
Potential Benefits:




Avoidance of
unnecessary clinical
interventions
Emotional - relief
Children can be
reassured
Avoidance of higher
insurance premiums
Potential Risks:



Adverse psychological
reaction (i.e. survivor guilt)
Dysfunctional family
dynamics
Complacent attitude to
health
Risks/Benefits/Limitations
of genetic testing?
Uninformative test result
Potential Benefits:




Future research may
clarify test results
Positive health behaviour
can be reinforced
Some relief
Higher insurance
premiums may be
avoided
Potential Risks:





Continue clinical
interventions which may
carry risks
Complacent attitude to
health
Uncertainty
Continued anxiety
Higher insurance premiums
may not be reduced
Legend
Breast cancer
Case: Rachel’s test
results….
Ovarian cancer
Rachel
BRCA1 185delAG
Normal
Mutation
What is the benefit of having genetic testing?
Can anything be done to change risk/outcome?

Recommendations for BRCA1 and BRCA2
mutation carriers:
 Lifestyle
Reduce dietary fat
 Avoid obesity
 Reduce alcohol consumption
 Regular exercise

Weak
Evidence
Recommendations for BRCA1 and BRCA2
mutation carriers
Breast
cancer surveillance
- Recommendations from Canadian Hereditary
Cancer Task Force, JOGC 2007
BSE – not recommended
CBE – part of surveillance program including imaging
Mammography & MRI (if available) q12 months age ≥30
MRI (possibly + U/S) if surveillance required before age 30
MRI may have higher sensitivity for surveillance of breast
cancer among BRCA1/2 carriers

2008 Meta-analysis: combined mammography and MRI screening
had a 94% sensitivity, 77% specificity (95% CI; p=0.01)
Recommendations for BRCA1 and BRCA2
mutation carriers

Ovarian cancer surveillance
- Recommendations from Canadian Hereditary
Cancer Task Force, JOGC 2007
 Surveillance not routinely recommended
 Women should be counselled on the limitations of
current screening for ovarian cancer
 If woman chooses surveillance, then consider the
following q6 months starting at age 30-35:
 pelvic exam
 transvaginal ultrasound
 serum CA-125
 Symptom recognition
Management of Mutation Carriers –
Surgical options: Risk reduction mastectomy
Recommendations from Canadian Hereditary Cancer Task
Force, JOGC 2007
 Potential benefits should be raised with all women with a
known mutation.
 Multidisciplinary team that includes at least: genetics
professional, breast surgeon, plastic surgeon.
 Women should have access to:




Written and oral information
Support services
Adequate time for reflection
Breast reconstruction options should be discussed in advance
Management of Mutation Carriers –
Surgical options: Risk reduction mastectomy

Hartmann et al. NEJM 1999






Retrospective study of 639 women with FH of breast cancer who
had bilateral mastectomy (mutation status unknown)
Expected 37 br ca in 425 women at mod risk (Gail model)
Observed 4 (90% risk reduction)
3 br ca in 214 high risk women with mastectomy (1.4%)
156 br ca in 403 sisters without mastectomy – 38.7% (90% risk
reduction)
Meijers-Heijboer et al. NEJM 2001


139 BRCA1 and BRCA2 mutation carriers
No br ca after 3 years in 76 ♀ with risk-reducing mastectomy
compared with 8 cases of br ca in 63 who chose surveillance
Management of Mutation Carriers –
Surgical options: risk reduction salpingooophorectomy (SO)
Recommendations from Canadian Hereditary Cancer
Task Force, JOGC 2007
 The potential benefits of risk reduction SO should be
discussed with women.
 Management by multidisciplinary team that includes a
genetics professional
 2009 meta-analysis Rebbeck et al.

80% reduction in risk of BRCA 1/2 -associated ovarian/fallopian
tube cancer


50% reduction in risk of breast cancer in BRCA 1/2 mutation
carriers


Hazard ratio 0.21 (95% CI = 0.12-0.39)
Hazard ratio 0.49 (95% CI = 0.37-0.65)
Optimal age of SO – more study needed
Management of Mutation Carriers Chemoprevention

Tamoxifen Prevention Trial 2005



Raloxifene



Shows promise
No data for mutation carriers
Aromatase inhibitors – ExCel trial



Invasive breast ca reduced from 42.5/1000 in placebo group to
24.8/1000 in Tamoxifen group in women at increased risk of
breast cancer
Preliminary data suggest benefit for BRCA2 but not BRCA1
carriers
Exemestane vs. placebo (Ca Info Service – 1-888-939-3333)
No data for mutation carriers
2007 Canadian Hereditary Cancer Task Force
Recommendations: women choosing chemoprevention
should be enrolled in a clinical trial
Management of Mutation Carriers
Consider…

Psychosocial support to assist with:
 Adjusting


to new information
most adjust within 3-6 months
subset remain psychologically distressed (16-25% anxiety
and/or depression)
 Making
decisions regarding management
“to inflict surgery is a hard decision to make… when I don’t
have the disease and feel healthy”
 Addressing
family issues, self concept, body image
 Dealing with future concerns i.e. child bearing,
surgical menopause after oophorectomy

Referral to support groups
Management of Mutation Carriers
Consider…

Additional psychosocial support may be needed
for high risk individuals such as those with:
 History
 Poor
of depression/anxiety
coping skills
 Inadequate
 Multiple
 Loss
social support / conflict in the family
losses in the family
of parent at a young age
 Recent
 Multiple
loss
surgical procedures
Testing children for BRCA1 and BRCA2 mutations

Benefits and non-harm



Autonomy



Consider the child’s autonomy and ability to provide informed
consent
Parents are not always the decision maker for a child
Privacy/confidentiality


No medical benefit from genetic testing for children < 18
Potential harm from this information – psychological, insurability, etc.
Results are available to the parent who may or may not share these
with the child
Equity & justice

Access to resources if the genetic status is known vs unknown
Despite focus on hereditary cancers…

Most women will not develop breast cancer
 Of
those who do, most will not have a known family
history

Increasing age is the greatest risk factor

Most women with family history of breast ca:
 do not fall into a high-risk category
 do not develop breast cancer
 are not eligible for genetic testing

All women should be “breast aware” and contact
their health care providers if any lumps or breast
changes are noted.
Cases
Assessing the Risk of Hereditary Breast Cancer
Using the Canadian Cancer Society triage card (below), what
category of risk do the following family histories fit into?
Legend
Case 1
Colon
Breast
Colon Ca Dx 76
died 85Aneurysm
Alz -75
A&W
A&W
Your Patient
↑Chol
A&W
Accident
BrCa Dx 68
Asthma
A&W
MI 80
BrCa Dx 61
Case 1
Legend
Colon
Breast
Case 1 Answer:
Moderate risk for hereditary breast cancer
 Two 1st/2nd degree relatives on the
same side of the family with breast cancer
< age 70
 Management:

 CBE
and mammogram q1 years starting at 40
 Discuss lifestyle changes
 Consider enrollment in chemoprevention
clinical trial
Legend
Case 2
Alz -75
Br Ca Dx 41
A&W
Breast
Accident
Stroke -83
A&W
Your Patient
↑Chol
A&W
IDDM
Asthma
A&W
MI 85
Migraines
Case 2
Legend
Breast
Case 2 Answer:

Moderate risk for hereditary breast cancer

One 1st/2nd degree relative with breast cancer at
35-49 years

Management:
 CBE
and mammogram q1 years staring at 40
 Discuss lifestyle changes
 Consider enrollment in chemoprevention clinical trial
Legend
Case 3
Prostate
Breast
Ovarian
Alz -75
A&W
Bilateral Breast Ca Dx 49
died 53 Aneurysm
OvCa Dx 52
Prost Ca 65
Your Patient
A&W
Accident
IDDM
Asthma
A&W
BrCa Dx 75
↑ Chol
Case 3
Legend
Prostate
Breast
Ovarian
Case 3 Answer:
High risk for hereditary breast/ovarian
cancer
 One 1st/2nd degree relative with:
bilateral breast cancer, first one before
age 50
ovarian cancer (any age)

Case 3 Answer: High risk

Management:
 Offer
genetics or familial cancer clinic referral
Pt. agrees: Familial Cancer Clinic will suggest
management
Pt. declines: Discuss management with familial
cancer clinic or manage as moderate risk
Referral to psychologist and/or support
group
 Discuss: lifestyle changes, enrollment in
chemoprevention clinical trials

Legend
Case 4
Colon
Breast
Colon Ca Dx 76
died 85Aneurysm
Alz -75
A&W
A&W
Your Patient
↑Chol
A&W
Accident
MI 69
↑Chol
A&W
Breast Ca 85
BrCa Dx 71
Case 4
Legend
Colon
Breast
Case 4 Answer:
Low risk for hereditary breast cancer
 Meets none of the high or moderate risk
criteria


Management:
 Clinical
breast exam & mammogram q 1-2
years beginning at age 50
 Discuss lifestyle changes
Legend
Case 5
Prostate
Breast
Ovarian
Nt Causes -75
A&W
Eastern Europe
Ashkenazi Jewish
Irish / German
Christian
Prost Ca Dx 80
Died 81
Died 81 stroke
Schizophrenic
Your Patient
OvCa Dx 52
MI 65
A&W
IDDM
Asthma
IDDM
BrCa Dx 55
↑ Chol
BrCa Dx 45
Case 5
Legend
Prostate
Breast
Ovarian
Case 5 Answer:
High risk for hereditary breast/ovarian cancer
 3 relatives on the same side of the family with
breast or ovarian cancer at any age
Management:
 Offer genetics or familial cancer clinic referral

 Agrees:
Familial Cancer Clinic will suggest
management
 Declines: Discuss management with familial cancer
clinic or manage as moderate risk


Referral to psychologist and/or support group
Discuss: lifestyle changes, enrollment in
chemoprevention clinical trials
Legend
Case 6
Bladder
Breast
Head & Neck
Neck CA
Dx 70
Bladder CA
Dx55
Bladder CA Dx 58
died 62
A&W
Your Patient
Head CA
Dx 65
A&W
Accident
Diabetes
Asthma
A&W
MI-84
BrCa Dx 61
Case 6
Legend
Bladder
Breast
Head & Neck
Case 6 Answer:

Low risk for hereditary breast cancer
 Meets

none of the high or moderate criteria
Patient’s family worked in a tannery and
shoe factory.
 Aromatic
amines (dyes) increase the risk of
bladder cancers
 Shoe manufacturers have an increase risk of
nasal cavity cancers
 The high incidence of cancer is due to
common environment exposures.
Resources

The National Cancer Institute:
http://cancernet.nci.nih.gov/
 Detailed





information on cancer for patients and
physicians including causes, treatments, clinical trials &
more
Canadian Cancer Society: www.cancer.ca
FORCE: www.facingourrisk.org
www.hereditarybreastcancer.cancer.ca
 Patient information aid
Gene Clinics: www.Genetests.org
 See Gene Reviews for clinical summaries
Where to find a genetics centre:
 www.cagc-accg.ca/centre1.html
The Genetics Education Project
Committee








June Carroll MD CCFP
Judith Allanson MD FRCP
FRCP(C) FCCMG FABMG
Sean Blaine MD CCFP
Mary Jane Esplen PhD RN
Sandra Farrell MD FRCPC
FCCMG
Judy Fiddes
Gail Graham MD FRCPC
FCCMG
Jennifer MacKenzie MD
FRCPC FAAP FCCMG







Wendy Meschino MD
FRCPC FCCMG
Joanne Miyazaki
Andrea Rideout MS CGC
CCGC
Cheryl Shuman MS CGC
Anne Summers MD
FCCMG FRCPC
Sherry Taylor PhD FCCMG
Brenda Wilson BSc MB
ChB MSc MRCP(UK)
FFPH
References
1.
Offit K 1998 Clinical Cancer Genetics: Risk Counseling
and Management. Wiley-Liss, New York.
2.
Daly MB, Bars Culver JO, Hull JL, Levy-Lahad E.
Overview of Breast Cancer Genetics at
www.genetests.org Last update September 11,
2003.Accessed on March 15, 2005.
3.
Statistics from the Canadian Cancer Society:
http://www.cancer.ca/ccs/internet/standard/0,3182,3172_
14435_371399_langId-en,00.html. Accessed on March
15, 2005.
4.
Lightning bolt photo credit:
http://www.ghouli.com/articles/sp/mainstream_4b.htm
References
5.
Seo, JH, Cho D-Y, Ahn S-H, Yoon K-S, Kang C-S, Cho
HM, Lee HS, Choe JJ, Choi CW, Kim BS, Shin SW,
Kim YH, Son G-S, Lee J-B, Koo BH. BRCA1 and
BRCA2 germline mutations in Korean patients with
sporadic breast cancer. Hum Mutat 2004; Online
Mutation in Brief #746.
6.
Ford D, Easton DF, Peto J. Estimates of the gene
frequency of BRCA1 and its contribution to breast and
ovarian cancer. Am J Hum Genet 1995; 57:1457-1462.
7.
Struewing JP, Hartge P, Wacholder S, Baker SM,
Berlin M, McAdams M, Timmerman MM, Brody LC,
Tucker MA. The risk of cancer associated with specific
mutations of BRCA1 and BRCA2 among Ashkenazi
Jews. N Engl J Med 1997; 336:1401-1408.
References
8.
Calderon-Margalt R, Paltiel O. Prevention of breast
cancer in women who carry BRCA1 or BRCA2
mutations: a critical review of the literature. Int J
Cancer 2004; 112:357-364.
9.
Tonin PN, Perret C, Lambert JA, Paradia A-J,
Kantemiroff T, Benoit M-H, Martin G, Foulkes W,
Ghadirian P. Founder BRCA1 and BRCA2 mutations
in early-onset French Canadian breast cancer cases
unselected for family history. Int J Cancer (Pred Oncol)
2001; 95: 189-193.
10.
Easton DF, Ford D, Bishop DT. And the Breast Cancer
Linkage Consortium. Breast and ovarian cancer
incidence in BRCA1 – mutation carriers. Am J Hum
Genet 1995; 56: 265-271.
References
11.
Satagopan JM, Offit K, Foulkes W, Robson ME,
Wacholder S, Eng CM, Karp SE, Begg CB. The
lifetime risks of breast cancer in Ashkenazi Jewish
carriers of BRCA1 and BRCA2 mutations. Cancer
Epidemiol Biomarkers Prev 2001; 10:467-473.
12.
Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord
JE, Hopper JL, Loman N, Olsson H, Johannsson O,
Borg A, Pasini B, Radice P, Manoukian S, Eccles DM,
Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J,
Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola
H, Nevanlinna H, Syrjakoski K, Kallioniemi O-P,
Thompson D, Evans C, Peto J, Lalloo F, Evans C,
Easton DF. Average risks of breast and ovarian cancer
associated with BRCA1 or BRCA2 mutations detected
in case series unselected for family history: a
combined analysis of 22 studies. Am J Hum Genet
2003; 72:1117-1130.
References
13.
Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P,
Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare
MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR,
Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder
BA, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D,
Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM,
Vassen H and the Breast Cancer Linage Consortium. Genetic
heterogeneity and penetrance analysis of the BRCA1 and BRCA2
genes in breast cancer families. Am J Hum Genet 1998; 62:676689.
14.
Risch HA, McLaughlin JR, Cole DEC, Rosen B, Bradley L, Kwan
E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JLA, Fan I,
Wong B, Narod SA. Prevalence and penetrance of germline
BRCA1 and BRCA2 mutations in a population series of 649
women with ovarian cancer. Am J Hum Genet 2001; 68:700-710.
References
15.
Liede A, Karlan BY, Narod SA. Cancer risks for male
carriers of germline mutations in BRCA1 or BRCA2: a
review of the literature. J Clin Oncol 2004; 22:735-742.
16.
Kirchhoff T, Kauff ND, Mitra N, Nafa K, Huang H,
Palmer C, Gulati T, Wadsworth E, Donat S, Robson
ME, Ellis NA, Offit K. BRCA mutations and risk of
prostate cancer in Ashkenazi Jews. Clin Cancer Res
2004; 10:2918-2921.
17.
Thompson D, Easton DF and the Breast Cancer
Linkage Consortium. Cancer incidence in BRCA1
mutation carriers. J Natl Cancer Inst. 2002; 94:13581365.
References
18.
Petrucelli N, Daly MB, Burke W, Bars Culver JO, Hull JL, LevyLahad E, Feldman GL. BRCA1 and BRCA2 Hereditary
Breast/Ovarian Cancer www.genetstests.org Last updated
September 3, 2004. Accessed March 15, 2005.
19.
Bermejo JL, Hemminki K. Risk of cancer at sites other than the
breast in Swedish families eligible for BRCA1 or BRCA2 mutation
testing. Ann Oncol 2004; 15:1834-1841.
20.
The Breast Cancer Linkage Consortium. Cancer risks in BRCA2
mutation carriers. J Natl Cancer Inst 1999; 91:1310-1316.
21.
Predictive Cancer Genetics Steering Committee. Ontario
physicians’ guide to referral of patients with family history of
cancer to a familial cancer genetics clinic or genetics clinic.
Ontario Medical Review 2001; 68:24-29.
References
22.
Pal Y, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H,
LaPolla J, Hoffman M, Martino M, Wakeley K, Wilbanks G,
Nicosia S, Cantor A, Sutphen R. BRCA1 and BRCA2 mutations
account for a large proportion of ovarian carcinoma cases. Cancer
2005; 104:2807-2816.
23.
Berg AO, Allan JD, Frame PS, Gordis L, Gregory KD, Harris R,
Johnson MS, Klein JD, Loveland-Cherry C, Moyer VA, Ockene
JK, Petitti DB, Siu AL, Teutsch SM, Yawn BP. U.S. Preventive
Services Task Force. Genetic risk assessment and BRCA
mutation testing for breast and ovarian cancer susceptibility:
recommendation statement. Ann Intern Med. 2005; 143;355-361.
24.
National Cancer Institute: Breast Cancer Prevention:
http://www.nci.nih.gov/cancertopics/pdq/prevention/breast/healthp
rofessional Accessed on April 4,2005.
References
25.
Horsman D, Wilson BJ, Avard D, Meschino WS, Sing CK, Plante
M, Eisen A, Howley HE, Simard J on behalf of the National
Hereditary Cancer Task Force. Clinical Management
Recommendations for Surveillance and Risk-Reduction
Strategies for Hereditary Breast and Ovarian Cancer Among
Individuals Carrying a Deleterious BRCA1 or BRCA2 Mutation. J
Obstet Gynaecol Can 2007;29:45–60.
26.
Warner E. Systematic Review: Using Magnetic Resonance
Imaging to Screen Women at High Risk for Breast Cancer Ann.
Intern. Med 2008;148:671.
27.
Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold
PG, Petty PM, Sellers TA, Johnson JL, McDonnell SK, Frost MH,
Jenkins RB. Efficacy of bilateral; prophylactic mastectomy in
women with a family history of breast cancer. N Engl J Med 1999;
340:77-82.
References
28.
Meijers-Heijboer H, van Geel B, van Putten WLJ, HenzenLogmans SC, Seynaeve C, Menke-Pluymers MBE,
Bartels CCM, Verhoog LC, van den Ouweland AMW,
Niermeijer MF, Brekelmans CTM, Klijn JGM. Breast
cancer after prophylactic mestomy in women with BRCA1
or BRCA2 mutations. N Engl J Med 2001; 345:159-164.
29.
American College of Obstetricians and Gynecologists.
ACOG Practice Bulletin: Hereditary breast and ovarian
cancer syndrome. Gynecol. Oncol. 2009;113:6-11.
30.
Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of
Risk Reduction Estimates Associated With Risk-Reducing
Salpingooophorectomy in BRCA1 or BRCA2 Mutation
Carriers JNCI 2009;101:80.
References
31.
Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin
WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese
RG, Runowicz CD James JM, Ford LG, Wolmark N. Tamoxifen
for the prevention of breast cancer: current status of the national
surgical adjuvant breast and bowel project P-1 study. J Natl
Cancer Inst. 2005; 97:1652-1662. Kote-Jarai Z, Powles, Mitchell
G, Tidy A, Ashley S, Easton D, Assersohn L, Sodha N, Salter J,
Gusterson B, Dowsett M, Eeles R. BRCA1/BRCA2 mutation
status and analysis of cancer family history in participants of the
Royal Marsden Hospital tamoxifen chemoprevention trial. Cancer
Lett. 2007;247:259-265.
32.
Prichard RS, Hill AD, Dijkstra B, McDermott W, O’Higgins NJ. The
prevention of breast cancer. Br J Surg 2003; 90: 772-783
33.
King M-C, Wieand S, Hale K, et al. Tamoxifen and breast cancer
incidence among women with inherited mutations in BRCA1 and
BRCA2: National surgical adjuvant breast and bowel project
(NASBP-1) breast cancer prevention trial. JAMA 2001;286:2372256.
References
34.
Kote-Jarai Z, Powles, Mitchell G, Tidy A, Ashley S, Easton D,
Assersohn L, Sodha N, Salter J, Gusterson B, Dowsett M, Eeles
R. BRCA1/BRCA2 mutation status and analysis of cancer family
history in participants of the Royal Marsden Hospital tamoxifen
chemoprevention trial. Cancer Lett. 2007;247:259-265.
35.
Narod SA, Brunet J-S, Ghadirian P, Robson M, Heimdal K,
Neuhausen SL, Stoppa-Lyonnet D, Lerman C, Pasini B, de los
Rios P, Weber B, Lynch H for the Hereditary Breast Cancer
Clinical Study Group. Tamoxifen and risk of contralateral breast
cancer in BRCA1 and BRCA2 mutation carriers: a case control
study. Lancet 2000; 356:1876-1881.