An Overview of Clinical An Overview of Clinical Cancer GeneticsCancer Genetics

MMónica Alvarado, MS, CGCónica Alvarado, MS, CGC

Certified Genetic CounselorCertified Genetic Counselor

Regional Administrator, Genetic ServicesRegional Administrator, Genetic Services

Kaiser Permanente, Southern CaliforniaKaiser Permanente, Southern California

New cases in U.S. each yearNew cases in U.S. each year Breast cancer:Breast cancer: >185,000>185,000 Colorectal cancer:Colorectal cancer: >150,000>150,000 Ovarian cancer:Ovarian cancer: > 25,000> 25,000If If 5% to 10%5% to 10% of these are due to hereditary cancer of these are due to hereditary cancer

syndromes then…Each year betweensyndromes then…Each year between 18,000 to 18,000 to 36,00036,000 newly diagnosed patients would be newly diagnosed patients would be appropriate for referral to a cancer genetic appropriate for referral to a cancer genetic counselorcounselor

Reports indicate that only about 5% to 7% of Reports indicate that only about 5% to 7% of patients who have a personal/family history of patients who have a personal/family history of cancer suggestive of hereditary cancer are ever cancer suggestive of hereditary cancer are ever referred for genetic counselingreferred for genetic counseling.

GENETIC vs. INHERITEDGENETIC vs. INHERITED

CANCER IS ALWAYS GENETICCANCER IS ALWAYS GENETIC BUT RARELY INHERITEDBUT RARELY INHERITED

Cancer Arises From Gene Cancer Arises From Gene MutationsMutations

Germline mutationsGermline mutations Somatic mutationsSomatic mutations

Somatic Somatic mutation (eg, mutation (eg,

breast)breast)

Mutation Mutation in egg or in egg or

spermsperm

All cells All cells affected in affected in offspringoffspring

ParentParent ChildChild

Present in egg or spermPresent in egg or sperm Are heritable Are heritable Cause cancer family Cause cancer family

syndromessyndromes

Occur in nongermline Occur in nongermline tissues tissues

Are nonheritableAre nonheritable

When to Suspect When to Suspect Hereditary Cancer SyndromeHereditary Cancer Syndrome Cancer in 2 or more close relatives Cancer in 2 or more close relatives

(on same side of family)(on same side of family) Early age at diagnosis (< 45 yrs)Early age at diagnosis (< 45 yrs) Multiple primary tumorsMultiple primary tumors Bilateral or multiple rare cancersBilateral or multiple rare cancers Constellation of tumors consistent with specific cancer Constellation of tumors consistent with specific cancer

syndrome (eg, breast and ovary, colon & endometrium)syndrome (eg, breast and ovary, colon & endometrium) Evidence of autosomal dominant transmissionEvidence of autosomal dominant transmission Triple negative breast cancer plus any one of the aboveTriple negative breast cancer plus any one of the above

Autosomal Dominant Autosomal Dominant InheritanceInheritance

Each child has 50% chance Each child has 50% chance of inheriting the mutationof inheriting the mutation

No “skipped generations”No “skipped generations”

Equally transmitted by Equally transmitted by men and womenmen and women

AffectedAffected

Normal Normal

SyndromeSyndrome GeneGene CancersCancers

Hereditary Breast/Ovarian

BRCA1 BRCA2

Breast, Ovarian, Pancreas, Others

Lynch Syndrome/Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

MLH1 MSH2 MSH6

PMS2

Colorectal (CRC), Endometrial,

Gastric, Ovarian, Other GI, Urinary tract

Familial Adenomatous Polyposis (FAP)

APCColorectal, Duodenal, Thyroid, Brain

Colorectal Cancer: >150,000Colorectal Cancer: >150,000 cases annually in the US cases annually in the US

SporadicSporadic (~60%) Familial (~30%)

HNPCC (3-5%)

FAP (<1%)FAP (<1%)

Rare syndromes (~4%)

Nat Med Nat Med 1996; 2:169-741996; 2:169-74

Familial Risk for Colorectal Familial Risk for Colorectal CancerCancer

ApproximatApproximatee

lifetime lifetime CRC risk to CRC risk to age 70 yrsage 70 yrs

(%)(%)

Affected family membersAffected family members

0

20

40

60

80

100

NoneNone One 1°One 1° One 1° One 1° and two and two

2°2°

One 1° One 1° age age <45<45

Two 1°Two 1° HNPCC HNPCC mutationmutation

2%2% 6%6% 8%8% 10%10%17%17%

70%70%

Aarnio M et al. Aarnio M et al. Int J CancerInt J Cancer 64:430, 1995 64:430, 1995 Houlston RS et al. Houlston RS et al. Br Med JBr Med J 301:366, 1990 301:366, 1990 St John DJ et al. St John DJ et al. Ann Intern Med Ann Intern Med 118:785, 1993 118:785, 1993

Lynch Syndrome (HNPCC)- About Lynch Syndrome (HNPCC)- About 3% of all Colorectal Cancer3% of all Colorectal Cancer

Early (but variable) onset of CRC:Early (but variable) onset of CRC: Average age of onset of CRC is 45 yearsAverage age of onset of CRC is 45 years

Defects in one of 4 mismatch repair genes:Defects in one of 4 mismatch repair genes: MLH1, MSH2, MSH6, PMS2MLH1, MSH2, MSH6, PMS2

Tumors tend to be Tumors tend to be right sidedright sided 90% or more of CRC tumors exhibit microsatellite 90% or more of CRC tumors exhibit microsatellite

instabilityinstability Muir-Torre syndrome is a variant of HNPCC Muir-Torre syndrome is a variant of HNPCC

associated with sebaceous adenomasassociated with sebaceous adenomas

Population Risk

By age 50By age 50

0.2%0.2%

By age 70By age 70

2%2%LS Risk >25%>25% 80%80%

Gastroenterology 1996;110:1020-7Int J Cancer 1999;81:214-8

LS Increases the Risk ofLS Increases the Risk ofColorectal CancerColorectal Cancer

Population RiskPopulation Risk

By age 50By age 50

0.2%0.2%

By age 70By age 70

1.5%1.5%LS RiskLS Risk 20%20% 60%60%

Gastroenterology Gastroenterology 1996;110:1020-71996;110:1020-7Int J CancerInt J Cancer 1999;81:214-8 1999;81:214-8

LS Increases the Risk of LS Increases the Risk of Endometrial CancerEndometrial Cancer

The Family History Is Key The Family History Is Key to Diagnosing LSto Diagnosing LS

CRCCRCdx 50sdx 50s

CRCCRCdx 45dx 45

CRCCRCdx 61dx 61

CRCCRCdx 75dx 75

OvarianOvarianCa, dx Ca, dx

6464

CRCCRCdx 48dx 48

CRCCRCdx 52dx 52

EndometriaEndometriall

Ca, dx 59Ca, dx 59

CRCCRCdx 42dx 42

4545

LS: Clinical Characteristics of LS: Clinical Characteristics of Colorectal CancerColorectal Cancer

Early age of diagnosisEarly age of diagnosis• mean age <45 yrsmean age <45 yrs

Predominantly proximal Predominantly proximal (right) colon cancer(right) colon cancer

Improved survivalImproved survival Patients develop similar Patients develop similar

numbers of adenomas as numbers of adenomas as the general populationthe general population

LS Cancer RisksLS Cancer Risks

Colorectal: Colorectal: Up to 80% lifetime risk Up to 80% lifetime risk Endometrial: 30% to 60% lifetime riskEndometrial: 30% to 60% lifetime risk Ovary: Ovary: 12% by age 7012% by age 70 Stomach: Stomach: 13% by age 7013% by age 70 OtherOther

• Urinary tract (4% by age 70)Urinary tract (4% by age 70)• Small intestine (100-fold relative risk, but < 5%)Small intestine (100-fold relative risk, but < 5%)• Biliary tract (2% by age 70)Biliary tract (2% by age 70)• Brain (~4% by age 70)Brain (~4% by age 70)

Gastroenterology Gastroenterology 1996;110: 1020-71996;110: 1020-7Int J CancerInt J Cancer 1999;81:214-8 1999;81:214-8

Management of LSManagement of LS

Colonoscopy Prevents Cancer in Colonoscopy Prevents Cancer in Mutation CarriersMutation Carriers

Gastroenterology 118:829, 2000Gastroenterology 118:829, 2000

Proportion free of Proportion free of CRCCRC

8080

6060

00 55 1010Follow-up time (years)Follow-up time (years)

4040

100100

1515

57.8%57.8%

No surveillanceNo surveillanceSurveillanceSurveillance

81.7%81.7%

Microsatellite Instability (MSI)Microsatellite Instability (MSI)

10% to 15% of sporadic tumors have 10% to 15% of sporadic tumors have MSIMSI

95% of LS colon tumors have MSI95% of LS colon tumors have MSI Can be used as a screening testCan be used as a screening test

If colorectal tumor is MSI-H and family If colorectal tumor is MSI-H and family history is positive for CRC very high history is positive for CRC very high likelihood of LSlikelihood of LS

IHC tumor test for LSIHC tumor test for LS

IHC Test & ResultsIHC Test & ResultsRationale for IHC tumor testRationale for IHC tumor test Universal IHC screening detects Universal IHC screening detects nearly twice as nearly twice as

many cases of LS as targeting younger patientsmany cases of LS as targeting younger patients Cost effectiveCost effective

can be internalizedcan be internalized results point to which MMR genes to analyzeresults point to which MMR genes to analyze

ResultsResults 80% all proteins present80% all proteins present

Most likely not LSMost likely not LS 20% one or more proteins absent20% one or more proteins absent

Most will not have LSMost will not have LS Approximately a third of these patients will test Approximately a third of these patients will test

positive for a MMR mutationpositive for a MMR mutation

2011 KPSC IHC Pilot Proposal2011 KPSC IHC Pilot Proposal Surgery Surgery

provide the “IHC fact sheet” to patients scheduled for CRC provide the “IHC fact sheet” to patients scheduled for CRC tumor surgerytumor surgery

PathologyPathology order reflex IHC testing on order reflex IHC testing on all CRCall CRC ≤ 50 yrs≤ 50 yrs at at

diagnosisdiagnosis(~185 to 200 cases/yr)(~185 to 200 cases/yr) Immunohistochemistry labImmunohistochemistry lab

performs IHC on tumor specimens per protocolperforms IHC on tumor specimens per protocol sends all abnormal IHC tumor results (~20% of cases) to sends all abnormal IHC tumor results (~20% of cases) to

surgeon surgeon andand local genetics contact local genetics contact GeneticsGenetics

Arranges follow-up of all abnormal IHC MMR results Arranges follow-up of all abnormal IHC MMR results including:including:• Contacts patient to offer genetics consultation as neededContacts patient to offer genetics consultation as needed• Coordinates follow-up tumor & germ line testing andCoordinates follow-up tumor & germ line testing and

appropriate counselingappropriate counseling

Lynch Syndrome: Key PointsLynch Syndrome: Key Points Most common form of hereditary CRC. Autosomal Most common form of hereditary CRC. Autosomal

Dominant inheritanceDominant inheritance About 3% or colorectal and endometrial cancersAbout 3% or colorectal and endometrial cancers Uterine/Endometrial cancer second most common Uterine/Endometrial cancer second most common

after CRC in HNPCC familiesafter CRC in HNPCC families Family/Personal history and IHC and/or MSI can Family/Personal history and IHC and/or MSI can

help identify affected individualshelp identify affected individuals Identifying individuals with LS can minimize impact Identifying individuals with LS can minimize impact

of disorder for them and their family membersof disorder for them and their family members High risk of multiple primary CRC and extra-intestinal tumorsHigh risk of multiple primary CRC and extra-intestinal tumors Colonoscopic surveillance can improve survival in at-risk Colonoscopic surveillance can improve survival in at-risk

individuals individuals For every individual identified with LS there are For every individual identified with LS there are approx. approx. 3 affected family members3 affected family members. Potential for preventing CRC . Potential for preventing CRC in unaffected personsin unaffected persons

Familial Adenomatous Familial Adenomatous Polyposis (FAP)Polyposis (FAP)

About 1% of all CRC; Incidence 1 in 8,000About 1% of all CRC; Incidence 1 in 8,000 Multiple colonic adenomas (100s) beginning in Multiple colonic adenomas (100s) beginning in

childhood or teen yearschildhood or teen years Autosomal dominant pattern of CRC: Autosomal dominant pattern of CRC:

Average age of CRC is 36Average age of CRC is 36 Risk of CRC by age 40 nearly 100%Risk of CRC by age 40 nearly 100%

Mutations in APC gene on 5qMutations in APC gene on 5q 80% are protein truncating mutations80% are protein truncating mutations

Up to 30% are Up to 30% are new mutationsnew mutations

Family with FAPFamily with FAP

Age 18Age 18APC+APC+FAP dx. 15FAP dx. 15SurveillanceSurveillance

Colon CAColon CAdx. 47dx. 47

Age 40Age 40APC -APC -

Age 45Age 45FAP, dx. 27FAP, dx. 27ColectomyColectomy

FAP, dx. 25FAP, dx. 25CRC dx. 31, d. 35CRC dx. 31, d. 35

Age 42Age 42FAP dx.38FAP dx.38APC+APC+ColectomyColectomy

Clinical Features of FAPClinical Features of FAP

Estimated penetrance Estimated penetrance for adenomas >90%for adenomas >90%

Risk of extracolonic Risk of extracolonic tumors (upper GI, tumors (upper GI, desmoid, osteoma, desmoid, osteoma, thyroid, brain, other)thyroid, brain, other)

CHRPE may be present CHRPE may be present

Untreated polyposis Untreated polyposis leads to 100% risk of leads to 100% risk of cancer cancer

Other Cancers Associated Other Cancers Associated with FAPwith FAP

Duodenal & periampullary cancer Duodenal & periampullary cancer 5-12 %5-12 % Thyroid cancerThyroid cancer 2 %2 % Pancreatic cancerPancreatic cancer 2 % 2 % Hepatoblastoma (childhood)Hepatoblastoma (childhood) 2 %2 % Gastric cancerGastric cancer 0.5 %0.5 % CNS tumorsCNS tumors <1 %<1 %

Burt, Burt, Gastroenterology Gastroenterology 2000; 119:837-53 2000; 119:837-53

Cancer RiskCancer Risk Lifetime RiskLifetime Risk

Gardner’s Syndrome:Gardner’s Syndrome:A Variant of FAPA Variant of FAP

Desmoid tumorsDesmoid tumors OsteomasOsteomas Dental abnormalitiesDental abnormalities CHRPECHRPE Soft tissue skin Soft tissue skin

tumorstumors

Features of FAP plus Features of FAP plus extraintestinal lesions:extraintestinal lesions: Epidermoid Epidermoid

cystcyst

Jaw osteomaJaw osteoma

Medical Management of FAPMedical Management of FAP

11GastroenterologyGastroenterology 2001; 121:197-7 2001; 121:197-722Steinbach, Steinbach, NEJMNEJM 2000; 342:1946-52 2000; 342:1946-52

Annual flexible sigmoidoscopy beginning at age 10Annual flexible sigmoidoscopy beginning at age 1011

Prophylactic total colectomy after polyp detectionProphylactic total colectomy after polyp detection chemoprevention: chemoprevention:

• celecoxib after surgerycelecoxib after surgery22

• NSAIDs (eg., sulindac) after surgery (investigational)NSAIDs (eg., sulindac) after surgery (investigational)

Subsequent surveillance for rectal and extracolonic Subsequent surveillance for rectal and extracolonic tumorstumors

FAP: Key PointsFAP: Key Points Autosomal dominant with early onset of Autosomal dominant with early onset of

polyposispolyposis However, up to 30% new mutations (no family hx)However, up to 30% new mutations (no family hx)

Severe polyposis makes it easier to identify Severe polyposis makes it easier to identify affected individualsaffected individuals

CRC risk is 100% in untreated patientsCRC risk is 100% in untreated patients Genetic testing identifies most APC mutation Genetic testing identifies most APC mutation

carrierscarriers Endoscopic surveillance and colectomy can Endoscopic surveillance and colectomy can

significantly improve survivalsignificantly improve survival Noncarriers can avoid anxiety and unnecessary Noncarriers can avoid anxiety and unnecessary

teststests Genetic testing of children has medical benefitGenetic testing of children has medical benefit

Tumor Suppressor GenesTumor Suppressor Genes

Normal genes Normal genes (prevent cancer)(prevent cancer)

1st mutation1st mutation(susceptible carrier(susceptible carrier))

2nd mutation or loss 2nd mutation or loss (leads to cancer)(leads to cancer)

BRCA1BRCA1

Approximately 1 in 500 women may be carriers of Approximately 1 in 500 women may be carriers of alterations in BRCA1alterations in BRCA1

Breast tumors tend to be Breast tumors tend to be triple negative (ER, PR triple negative (ER, PR and Her2Neu negative),and Her2Neu negative), basal type, excess of basal type, excess of medullarymedullary

Ovarian tumors: epithelial, high grade, mucinous Ovarian tumors: epithelial, high grade, mucinous and borderline tumors rareand borderline tumors rare

Specific alterations observed in ~1% Ashkenazi Specific alterations observed in ~1% Ashkenazi Jewish individuals: 185delAG, 5382insCJewish individuals: 185delAG, 5382insC

BRCA2BRCA2 Gene is twice the size of BRCA1Gene is twice the size of BRCA1 Breast tumors tend to be ER +, and no Breast tumors tend to be ER +, and no

specific histopathology observed specific histopathology observed Ovarian tumors: epithelial, high grade, Ovarian tumors: epithelial, high grade,

mucinous and borderline tumors raremucinous and borderline tumors rare Wider spectrum of cancer typesWider spectrum of cancer types Specific alteration in 1.5% of Ashkenazi Specific alteration in 1.5% of Ashkenazi

Jewish individuals: 6174delTJewish individuals: 6174delT

BRCA1 and BRCA2 in Ashkenazi BRCA1 and BRCA2 in Ashkenazi Jewish IndividualsJewish Individuals

1 in 40 will have mutation in BRCA1/2 1 in 40 will have mutation in BRCA1/2 regardless of family historyregardless of family history

Founder effect: 3 mutations account for Founder effect: 3 mutations account for the majority of carriersthe majority of carriers

Ashkenazi Jewish heritage Ashkenazi Jewish heritage mustmust be be identified for proper risk assessment and identified for proper risk assessment and mutation analysismutation analysis

The BRCA1 and 2 GenesThe BRCA1 and 2 Genes

BRCA1 & BRCA2BRCA1 & BRCA2-Associated -Associated Cancers: Lifetime RiskCancers: Lifetime Risk

breast cancer (often < 50 yrs)40%85%

Contralateral breast cancer40-60%

ovarian cancer 10%0%

male breast cancer elevated (6%)Pancreas & prostate cancers

may also be elevated

By age 30By age 30 By age 50By age 50 By age By age 7070

BRCA1/2 Mutations Increase Risk BRCA1/2 Mutations Increase Risk of Breast and Ovarian Cancerof Breast and Ovarian Cancer

Breast CancerBreast Cancer

Population RiskPopulation Risk <0.5%<0.5% ~2%~2% ~7%~7%

BRCA Carrier RiskBRCA Carrier Risk 2 - 3%2 - 3% 12 - 50%12 - 50% 40-85%40-85%

Ovarian CancerOvarian Cancer

Population RiskPopulation Risk <<<1%<<<1% <1%<1% 1%1%

BRCA Carrier RiskBRCA Carrier Risk <<1%<<1% 2 - 20%2 - 20% 15 - 45%15 - 45%

Identification of women at Identification of women at high risk for HBOChigh risk for HBOC

Family History & PresentationFamily History & Presentation Two or more cases of breast and/or ovarian cancer on same Two or more cases of breast and/or ovarian cancer on same

side of the familyside of the family Consider both sides of the family, ethnicityConsider both sides of the family, ethnicity

• Ashkenazi Jewish heritageAshkenazi Jewish heritage Early age of onset, multiple primaries, TNBCEarly age of onset, multiple primaries, TNBC

• Breast cancer <45 yrs at diagnosisBreast cancer <45 yrs at diagnosis• Breast & ovarian cancer in the same woman, multiple breast primariesBreast & ovarian cancer in the same woman, multiple breast primaries• TNBC: ER, PR and Her2 negative (BRCA1)TNBC: ER, PR and Her2 negative (BRCA1)

Autosomal dominant pattern of cancerAutosomal dominant pattern of cancer

Adapted from Myriad GeneticsAdapted from Myriad Genetics

Management of BRCA Mutation Management of BRCA Mutation Positive PatientPositive Patient

Positive Positive BRCA1 or BRCA2BRCA1 or BRCA2

MutationMutation

LifestyleLifestyleChangesChanges

IncreasedIncreasedSurveillanceSurveillance

ProphylacticProphylacticSurgerySurgery

Chemo-Chemo-preventionprevention

Offer test toOffer test torelativesrelatives

BRCA Carriers: Cancer ScreeningBRCA Carriers: Cancer ScreeningBreast cancer screening Monthly BSE from age 18Monthly BSE from age 18 Clinical breast exam 2-4 times per year (beginning at Clinical breast exam 2-4 times per year (beginning at

age 25)age 25) Annual Annual mammography and MRImammography and MRI starting at age 25 or starting at age 25 or

individualized based on earliest age of onset in familyindividualized based on earliest age of onset in family MRI is most sensitive imaging modality for surveillance of BRCA MRI is most sensitive imaging modality for surveillance of BRCA

carriers. 80% to 92% MRI vs 23% to 33% Mammo (based on 4 carriers. 80% to 92% MRI vs 23% to 33% Mammo (based on 4 studies, N=714)studies, N=714)

Ovarian cancer screening Concurrent TVU, Pelvic exam and CA125 q6 months Concurrent TVU, Pelvic exam and CA125 q6 months

starting at age 35 or 5-10 years earlier than earliest starting at age 35 or 5-10 years earlier than earliest onset in familyonset in family

No proven benefitNo proven benefit

Prophylactic Surgery in BRCA1/2 Prophylactic Surgery in BRCA1/2 carrierscarriers

Prophylactic mastectomyProphylactic mastectomy Reduces risk by ~90%Reduces risk by ~90% Total (simple) mastectomy recommendedTotal (simple) mastectomy recommended

• Nipple sparing mastectomy may be good alternativeNipple sparing mastectomy may be good alternative Risk-reducing salpingo-oopherectomyRisk-reducing salpingo-oopherectomy

Reduces risk by 85%-95% or moreReduces risk by 85%-95% or more• Must remove ovaries and tubes; hysterectomy currently Must remove ovaries and tubes; hysterectomy currently

optional in most centersoptional in most centers• Peritoneal washings recommended due to high incidence of Peritoneal washings recommended due to high incidence of

occult malignancyoccult malignancy Breast cancer risk reductionBreast cancer risk reduction

• 55-70% if done pre-menopausally55-70% if done pre-menopausally Does not eliminate risk for primary peritoneal cancerDoes not eliminate risk for primary peritoneal cancer

• Residual risk reported as 1% to 4.3%Residual risk reported as 1% to 4.3%

Chemoprevention for BRCA1/2 Chemoprevention for BRCA1/2 CarriersCarriers

Breast Cancer Tamoxifen & Raloxifene: Very little data on carriers; few choose it

Tamoxifen may be less effective in BRCA1 carriers One case control study reported ~50% contralateral cancer risk

reduction from Tamoxifen use in BRCA1/2 carriers No evidence that Tamoxifen post BSO reduces breast cancer risk

Ovarian Cancer Oral Contraceptives reduce risk by 50% to 70% with 5 yr use Data unclear: two large studies reached opposite conclusions on effects

of OCs in ovarian cancer risk for BRCA1/2 carriers Use should be evaluated on case by case basis

Narod et al, Lancet, 2000

BRCA Carriers: Timing can BRCA Carriers: Timing can influence decision makinginfluence decision making

How might a newly How might a newly diagnosed breast diagnosed breast cancer patient alter her cancer patient alter her treatment decisions?treatment decisions?

Surgery?Surgery? Chemotherapy?Chemotherapy?

How might her future How might her future cancer risk for cancer cancer risk for cancer influence these influence these decisions?decisions?

Second breast cancer?Second breast cancer? Ovarian cancer?Ovarian cancer?

52 50

d. 53Breast CAdx. 42

49Breast CAdx. 49BRCA2 +

d. 59Breast CAdx. 54

73 Breast CAdx. 60

29 27

Could this be HBOC?Could this be HBOC? How does Ashkenazi How does Ashkenazi

Jewish background affect Jewish background affect probability of mutation in probability of mutation in BRCA1 & 2?BRCA1 & 2? Non Ash.: 1.1%-5.6%Non Ash.: 1.1%-5.6% Ash. Jewish: 8.2%-15.6%Ash. Jewish: 8.2%-15.6%

How might cousin’s How might cousin’s TAH/BSO affect family TAH/BSO affect family history of breast and history of breast and ovarian cancer in this ovarian cancer in this family?family?

53 43 41 34TAH/BSO @ 45

d. 68 70

Unk CAd. 52

d. 53Ovarian CAdx. 51

d.70s

Polish/Hungarian Jewish

HBOC: Key PointsHBOC: Key Points Clues in the personal or family history of cancer Clues in the personal or family history of cancer

can help identify individuals who may have an can help identify individuals who may have an inherited susceptibility to breast or ovarian cancer inherited susceptibility to breast or ovarian cancer

Mutations in BRCA1/2:Mutations in BRCA1/2: Can be passed down from the mother or fatherCan be passed down from the mother or father Are far more frequent in Ashkenazi Jewish familiesAre far more frequent in Ashkenazi Jewish families Are inherited in autosomal dominant fashionAre inherited in autosomal dominant fashion

Genetic testing is offered only when personal Genetic testing is offered only when personal and/or family history of cancer suggests inherited and/or family history of cancer suggests inherited susceptibilitysusceptibility

Genetic testing can identify mutations in BRCA1/2 Genetic testing can identify mutations in BRCA1/2 and influence risk management, and save livesand influence risk management, and save lives

Cancer Genetics ResourcesCancer Genetics Resources FORCE:Facing Our Risk of Cancer Empowered; support FORCE:Facing Our Risk of Cancer Empowered; support

group for BRCA1/2 group for BRCA1/2

www.facingourrisk.orgwww.facingourrisk.org Cancer Genetics Services Directory: Cancer Genetics Services Directory:

http://cnetdb.nci.nih.gov/genesrch.shtmlhttp://cnetdb.nci.nih.gov/genesrch.shtml Johns Hopkins Digestive Disease Library:Johns Hopkins Digestive Disease Library:

www.hopkins-gi.orgwww.hopkins-gi.org CDC Colorectal Cancer:CDC Colorectal Cancer:

www.cdc.gov/cancer/colorctl/calltoaction/index.htmwww.cdc.gov/cancer/colorctl/calltoaction/index.htm Genetics of Cancer: Genetics of Cancer: www.cancergenetics.orgwww.cancergenetics.org