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Hereditary Breast/Ovarian Cancer PowerPoint PPT Presentation


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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

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Hereditary breast ovarian cancer l.jpg

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 l.jpg

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 l.jpg

Outline

  • Sporadic versus familial cancer

  • Hereditary breast cancer syndromes

  • Referral guidelines

  • Benefits, risks and limitations of genetic testing

  • Management

  • Cases


Cancer l.jpg

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


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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


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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


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Proportion of Hereditary Breast Cancer

Familial 10-15%

Hereditary 5-10%

Sporadic 80%


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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

Two mutations - one in each gene

CANCER


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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

Two mutations - one in each gene

CANCER


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Compared to sporadic cancer, people with hereditary cancer have…

  • A higher risk of developing cancer

  • A younger age of onset of cancer

    • Generally < 50 years of age

  • Multiple primary cancers

    Hereditary cancer is less common in the general population than sporadic cancer


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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

    • ~1/500 – 1/1,000 in general (Caucasian) population

    • 1/40 - 1/50 in Ashkenazi Jewish people

      • 3 common mutations in Ashkenazi Jews

    • Unique French Canadian mutations


Slide12 l.jpg

Autosomal Dominant Inheritance

Legend

B:BRCA gene with mutation

b: normal BRCA gene

Normal BRCA genes

BRCA mutation

bb

Bb

bb

Bb

Bb

bb

Population

Risk

Susceptible

BRCA gene

Susceptible

BRCA gene

Population

Risk


Brca1 and brca2 what happens when their function is compromised l.jpg

BRCA1 and BRCA2What 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


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Consequences of having a BRCA mutation:Estimated cancer risk by age 70


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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


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…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


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Case: Rachel

  • Rachel - healthy 40 year old

    • Concerned about her risk for cancer

    • Family history of both breast & ovarian cancer


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LEGEND

Breast cancer

Ovarian cancer

Case: Rachel’s family history

Ov Ca

Died 48

Br Ca

Dx 38

Ov Ca

Dx 40

RACHEL

age 40

Br Ca

Dx 30


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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


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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


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A genetics consultation involves:

  • Assessment of eligibility for genetic testing

    • Estimated risk of a mutation must be ≥10%

      for most provincial programs

    • Most appropriate family member to test first

  • 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


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Genetic Testing

  • Available at regional genetic centres and familial cancer clinics

  • Covered by provincial insurance plans (i.e. OHIP) if criteria are met:

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


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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


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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 testingPositive test result


Risks benefits limitations of genetic testing negative test result l.jpg

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?Negative test result


Risks benefits limitations of genetic testing uninformative test result l.jpg

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

Risks/Benefits/Limitations of genetic testing?Uninformative test result


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Legend

Breast cancer

Ovarian cancer

Case: Rachel’s test results….

Rachel

BRCA1185delAG

Normal

Mutation


What is the benefit of having genetic testing can anything be done to change risk outcome l.jpg

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


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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 carriers30 l.jpg

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


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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


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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 salpingo oophorectomy so l.jpg

Management of Mutation Carriers –Surgical options: risk reduction salpingo-oophorectomy (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

      • Hazard ratio 0.21 (95% CI = 0.12-0.39)

    • 50% reduction in risk of breast cancer in BRCA 1/2 mutation carriers

      • Hazard ratio 0.49 (95% CI = 0.37-0.65)

    • Optimal age of SO – more study needed


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Management of Mutation Carriers - Chemoprevention

  • Tamoxifen Prevention Trial 2005

    • 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

  • Raloxifene

    • Shows promise

    • No data for mutation carriers

  • Aromatase inhibitors – ExCel trial

    • 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 l.jpg

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


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Management of Mutation Carriers Consider…

  • Additional psychosocial support may be needed for high risk individuals such as those with:

    • History of depression/anxiety

    • Poor coping skills

    • Inadequate social support / conflict in the family

    • Multiple losses in the family

    • Loss of parent at a young age

    • Recent loss

    • Multiple surgical procedures


Testing children for brca1 and brca2 mutations l.jpg

Testing children for BRCA1 and BRCA2 mutations

  • Benefits and non-harm

    • No medical benefit from genetic testing for children < 18

    • Potential harm from this information – psychological, insurability, etc.

  • Autonomy

    • Consider the child’s autonomy and ability to provide informed consent

    • Parents are not always the decision maker for a child

  • Privacy/confidentiality

    • 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 l.jpg

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 l.jpg

Cases


Slide40 l.jpg

Assessing the Risk of Hereditary Breast CancerUsing the Canadian Cancer Society triage card (below), what category of risk do the following family histories fit into?


Case 1 l.jpg

Legend

Colon

Breast

Case 1

Colon Ca Dx 76

died 85Aneurysm

Accident

MI 80

Alz -75

↑Chol

BrCa Dx 68

A&W

BrCa Dx 61

A&W

A&W

Your Patient

A&W

Asthma


Case 142 l.jpg

Legend

Colon

Breast

Case 1


Case 1 answer l.jpg

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


Case 2 l.jpg

Legend

Breast

Case 2

Accident

MI 85

Alz -75

Stroke -83

↑Chol

IDDM

A&W

Br Ca Dx 41

A&W

A&W

Migraines

Asthma

Your Patient

A&W


Case 245 l.jpg

Legend

Breast

Case 2


Case 2 answer l.jpg

Case 2 Answer:

  • Moderaterisk 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


Case 3 l.jpg

Legend

Prostate

Breast

Ovarian

Case 3

Bilateral Breast Ca Dx 49

died 53 Aneurysm

Accident

BrCa Dx 75

Alz -75

Prost Ca 65

IDDM

A&W

A&W

OvCa Dx 52

↑ Chol

Asthma

Your Patient

A&W


Case 348 l.jpg

Legend

Prostate

Breast

Ovarian

Case 3


Case 3 answer l.jpg

Case 3 Answer:

  • Highrisk 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 l.jpg

Case 3 Answer: Highrisk

  • 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


Case 4 l.jpg

Colon

Breast

Legend

Case 4

Colon Ca Dx 76

died 85Aneurysm

Accident

Breast Ca 85

Alz -75

↑Chol

MI 69

A&W

A&W

A&W

BrCa Dx 71

Your Patient

A&W

↑Chol


Case 452 l.jpg

Colon

Breast

Legend

Case 4


Case 4 answer l.jpg

Case 4 Answer:

  • Lowrisk 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


Case 5 l.jpg

Legend

Prostate

Breast

Ovarian

Case 5

Eastern Europe

Ashkenazi Jewish

Irish / German

Christian

Prost Ca Dx 80

Died 81

BrCa Dx 55

Nt Causes -75

Died 81 stroke

MI 65

IDDM

IDDM

A&W

Schizophrenic

↑ Chol

BrCa Dx 45

Asthma

Your Patient

OvCa Dx 52

A&W


Case 555 l.jpg

Legend

Prostate

Breast

Ovarian

Case 5


Case 5 answer l.jpg

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


Case 6 l.jpg

Legend

Bladder

Breast

Head & Neck

Case 6

Neck CA

Dx 70

Bladder CA Dx 58

died 62

Accident

MI-84

Head CA Dx 65

Diabetes

A&W

BrCa Dx 61

Bladder CA Dx55

A&W

Your Patient

A&W

Asthma


Case 658 l.jpg

Legend

Bladder

Breast

Head & Neck

Case 6


Case 6 answer l.jpg

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 l.jpg

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 l.jpg

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

The Genetics Education Project Committee


References l.jpg

References

  • Offit K 1998 Clinical Cancer Genetics: Risk Counseling and Management. Wiley-Liss, New York.

  • 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.

  • 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.

  • Lightning bolt photo credit: http://www.ghouli.com/articles/sp/mainstream_4b.htm


References63 l.jpg

References

  • 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.

  • 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.

  • 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.


References64 l.jpg

References

  • 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.

  • 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.

  • 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.


References65 l.jpg

References

  • 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.

  • 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.


References66 l.jpg

References

  • 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; 62:676-689.

  • 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.


References67 l.jpg

References

  • 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.

  • 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.

  • Thompson D, Easton DF and the Breast Cancer Linkage Consortium. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002; 94:1358-1365.


References68 l.jpg

References

  • Petrucelli N, Daly MB, Burke W, Bars Culver JO, Hull JL, Levy-Lahad E, Feldman GL. BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer www.genetstests.org Last updated September 3, 2004. Accessed March 15, 2005.

  • 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.

  • The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999; 91:1310-1316.

  • 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.


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References

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