Presentation on theme: "Breast Cancer Risk Assessment and Genetic Testing"— Presentation transcript:
1Breast Cancer Risk Assessment and Genetic Testing Susan W. Caro, RNC, MSN, APNGDirector, Family Cancer Risk ServiceVanderbilt-Ingram Cancer Center
2Objectives:1. Appreciate the complex and emerging information about the impact of genetics on breast cancer risk.2. Identify resources available for assessing genetic risk.3. Articulate when risk counseling and assessment is recommended.4. Know the TN resources for genetic risk assessment.
3In 1990, the National Institutes of Health and the Dept In 1990, the National Institutes of Health and the Dept. of Energy launched the Human Genome Project, an international effort to map, sequence, and characterize the human genome. Working draft completed in June 2000, published in Science and Nature in February 2001.
4Why?Hereditary cancer syndromes are being more clearly defined with increasingly clear recommendations for management.Clinical genetics tests for hereditary cancer syndromes are available and in some markets are being marketed directly to the consumer.Recognizing hereditary cancer syndromes provides the opportunity to identify those at significantly increased risk and offer options to identify cancers earlier or prevent cancer in these individuals.Potential for medico-legal implications of not recognizing hereditary cancer syndromes.Lynch HT, Paulson JD, Severen M, et al. Failure to Diagnose Hereditary Colorectal Cancer and Its Medicolegal Implications. Dis. Colon Rectum January 1999;42:31-35.
5Hereditary Cancer Burden in Tennessee? Breast Cancer ,720 new diagnoses920 deathsColorectal Cancer ,290 new diagnoses1130 deathsIf ~10% hereditary cancer – 372 new cases of hereditary breast cancer (392 CRC) this year.Could some of these have been foreseen,even prevented?*Excludes carcinoma in situ (CIS, non-invasive cancer) of any site except urinary bladder.Does not include basal and squamous cell skin cancers (of which there are 1.3 million per year).American Cancer Society, 2008
6Prevention (medical)In medicine, prevention is any activity which reduces the burden of mortality or morbidity from disease. This takes place at primary, secondary and tertiary prevention levels.Primary prevention avoids the development of a disease. Most population-based health promotion activities are primary preventive measures.Secondary prevention activities are aimed at early disease detection, thereby increasing opportunities for interventions to prevent progression of the disease and emergence of symptoms.Tertiary prevention reduces the negative impact of an already established disease by restoring function and reducing disease-related complications.Wikipedia
7All cancer is genetic, not all cancer is hereditary.
8Breast Cancer Genes Found BRCA1 (for BReast CAncer gene 1) was described in 1990 on chromosome 17, isolated in 1994BRCA2 was isolated on chromosome 13 in late 1994BRCA3?
10American Society of Clinical Oncology Guidelines for Genetic Testing Personal or family history features suggestive of hereditary cancer riskTest can be adequately interpretedTest result will aid in diagnosis or influence medical management of the patient and/or familySlide 19: Guidelines for Cancer Predisposition TestingFor an individual whose personal and/or family history suggests the possibility of a hereditary melanoma syndrome, only a genetic test can confirm whether he/she carries a mutation in the p16 gene. The American Society of Clinical Oncology (ASCO) has recommended that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer.1 These criteria can be applied to identify appropriate candidates for genetic testing for hereditary melanoma.Reference:1. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol. 2003;21(12):J Clin Oncol 2003;21:
11Cancer Syndromes Hereditary Breast Cancer Syndromes BRCA1, BRCA2, Cowden, CHEK2, Li-FraumeniHereditary Colorectal Cancer SyndromesHNPCCFAPEndocrine Syndromes – VHL, MEN1, MEN2, FMTCOther – Li Fraumeni, Peutz-JeghersDNA Banking
12Ask – out loudAsk the question: Do you have a family history of cancer?Clarify - maternal AND paternal family historyAsk the question again more specifically: Does anyone in your family have a history of breast, ovarian, colon cancer, colon polyps, or other cancers?Ask the question again at follow up visits, as family histories change over time.FCRS
13Listen when your patients voice a concern: In many health care encounters today, we are focused on the problem at hand and it is difficult to go beyond this.Not suggesting that every health care provider have an expert knowledge of the complex issues surrounding all of the hereditary cancer syndromes - rather that continual exposure to this information will prompt recognition and referral for more thorough evaluation of the family.A significant number of our patients seek consultation independently. Their health care providers do not always recognize the significance of family history.
14ReferRefer for comprehensive risk assessment and consideration of genetic testing.Genetic testing is only one aspect of this. There is a great deal to be learned from gathering and documenting the family history and the educational component of the counseling process.Many patients are concerned as a result of things they have read or been told about insurance discrimination. This is addressed in the counseling session (before any decision for genetic testing is made).
15Family Cancer Risk Consultation Should include:Education about cancer risk in familiesCancer/genetic risk assessmentDiscussion of possible risks and benefits of genetic testingPsychological support, guidance about medical options, and referral for medical or surgical means of early detection or prevention of cancerOffit, 1998, p. 3
16Comprehensive Risk Assessment / Consultation Assess patient’s view of their risk, experience with cancer in the familyReview what is known and not known about cancer riskMedical history, current surveillance activityReview family history and draw pedigreeDocument cancers in history (medical record and pathology review)Provide risk assessment - Risks associated with hereditary cancer syndromes under consideration, risks if no recognizable syndromeEducation - Cancers, risks factors, surveillance, basic genetics, cancer geneticsTesting? Benefits, limitations, risks, costs, insurance, processRecommendations for surveillance or possible preventive measures, discuss implications to others in family.Interpretation of test results, including psychological, social, and family implications of test results
17Management Options / Counseling Review options for increased screening or measures to decrease riskDiscuss efficacy (or lack of efficacy/ or lack of data to support efficacy) of surveillance, prophylactic / risk reducing, or chemopreventive measuresIncreasing understanding of utility and consequences of surveillance and intervention options – a moving target.
18How Much Breast and Ovarian Cancer Is Hereditary? ASCO Curriculum: Cancer Genetics & Cancer Predisposition TestingHow Much Breast and Ovarian Cancer Is Hereditary?15%20%5%–10%5%–10%Breast CancerOvarian CancerSporadicFamily clustersHereditaryASCOBreast and Ovarian Cancer3
19Breast and ovarian cancers Contribution of BRCA1/2 to hereditary breast /ovarian cancer families:Breast Cancer FamiliesBreast and ovarian cancersBreast and OvarianCancer FamiliesKing, Rowell, Love, 1993; Ford, Easton, Stratton, et al, 1998
20BRCA Mutations and Ashkenazi Jews 185delAG mutation noted in 1% of 850 samples of Ashkenazi Jewish individuals unselected for family history of cancer (studied stored samples from Tay-Sachs research)Carrier rate 3 X that expected in general populationMay account for 16% of breast and 39% of ovarian cancer in AJ women <502 other “founder mutations”
21Male Breast Cancer and BRCA2 Studies of BRCA2 in population- and clinic-based series of male breast cancer patients from the United States and Europe have found carrier frequencies of BRCA2 mutations of 4% - 40%The percentage of male breast cancer cases that are associated with a BRCA2 mutation varies depending on the population. Figures from various studies (some small):4% in U.S.;21% in Sweden;40% in Iceland.One study showed that among men with breast cancer and a first-degree relative (e.g., mother or sister) with breast cancer approximately 11% were carriers of a BRCA2 mutation.For male BRCA2 alteration carriers:Estimated cumulative risk of male breast cancer is ~6% by age 70Age of onset not as early as female breast cancer in BRCA2 carriersBRCA1 may account for more cases of male breast cancer than initially estimated.(Couch et al. 1996, Thorlacius et al. 1996, Friedman et al. 1997, Csokay et al. 1999)
22Cumulative Risk of Breast and Ovarian Cancer in BRCA1 and BRCA2 Mutation CarriersFrom Rebbeck,T; J Clin Oncol 18:100s-103s 2000
23Risks of Breast Cancer with BRCA1 or BRCA2 Mutation Breast cancer risk by age (women)BRCA1BRCA2Ashkenazi women w/ BRCA1/2General population US4019%12%5050%28%33%2%6064%48%7085%84%56%7%Easton DF, Ford D, Bishop T, and the Breast Cancer Linkage Consortium, Am J Hum Gen 56:Easton DF, et al., and the Breast Cancer Linkage Consortium, JNCI 91:Ford D, Easton DF, Stratton M, Narod S, et al., 1998, Am J Hum Genetics 62:Struewing JP, Harge P, Wacholder W, et al. NEJM, (20):Ford D, Easton DG, Bishop T, Narod S, Lancet 343:
24Contralateral Breast Cancer Risk BRCA1/2 Mutation Carriers BRCA1 or BRCA2Women w/ prior hx breast cancerRisk of new breast ca dx by age 7060%52%3%/year<1% per year
25Recognition: the first step in management of familial cancer risk The hope is that increased surveillance and/or interventions may identify cancers early or reduce the risk of cancers.Risk assessment may also identify those not at increased risk.
26Cancer Clusters Cancer can happen in a family just by chance Cancer can cluster in families because of shared environmental exposures (diet, lifestyle, “environment”, work related exposures)Cancers may be due to inheritance of a single genetic alteration that poses very high risk of cancerCancers may be due to inheritance of less penetrant genetic alterations
27Sporadic/Familial/Hereditary Sporadic cancersAge appropriateCommon cancersFamilial CancerOccurring in or affecting more members of a family than would be expected by chance” Generally, two or more family members with the same type of cancer, age appropriateHereditary Cancer-Multiple affected family membersSeveral cases of the same type of cancer or cancers known to be part of an hereditary cancer syndrome (e.g. breast & ovarian, colon & endometrial, sarcoma & breast).Younger than expected ages of onset - such as breast < 40, colon < 50Rare cancers in the family such as males with breast cancerIndividuals with multiple primary cancers or multifocal or bilateral cancersFamily history consistent with generation to generation transmission
28Tools for risk assessment: Breast cancer risk assessment models - Claus, Gail, BRCAPRO, Frank/Myriad modelsModels for other cancers from the literatureComputer/Internet resourcesGene tests, OMIM, NCI websiteOngoing education
29Models used to calculate breast cancer risks Claus Model - Age specific risk estimates for breast cancer, considers maternal and paternal history, age at onset, first and second degree relatives (excludes some relatives).Gail Model - Estimates the chance that a woman of specific age would develop breast cancer, includes age at menarche, childbirth, # of prior biopsies, and first degree relatives. Excludes paternal relatives, non-first degree relatives. Adapted to consider atypical hyperplasias.Tyrer-Cusick Model – (2004) Uses personal risk factors for breast cancer, and likelihood of BRCA gene mutation and a low penetrance gene to assess breast cancer risk.Claus EB, Risch N, Thompson WD, 1990;1991;1994;Gail MH, Brinton LA, Byar EP, et al, 1989; Tyrer J, Duffy SW, Cuzick J. Stat Med 2004; 23:FCRS
30Models used to calculate likelihood of BRCA1 or BRCA2 mutation: BRCAPRO - computer model, uses pedigree to calculate risk based on several different models.Frank or Myriad Model/Tables - use family history and personal history to estimate risk of mutation in BRCA1 or BRCA2.BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) – University of Cambridge computer model to assess risk of BRCA1/2 mutation.Euhus D, Berry D, Parmigiani G, Iverson E, 1998; Frank TS, Manley SA, Olopade OI, et al, 1997, Antoniou AC, Hardy R, Walker L, Evans DG, Shenton A, Eeles R, Shanley S, Pichert G, Izatt L, Rose S, Douglas F, Eccles D, Morrison PJ, Scott J, Zimmern RL, Easton DF, Pharoah PD.J Med Genet Jul;45(7): Epub 2008 Apr 15.
31Characteristics of those families appropriate for consideration for BRCA1 or BRCA2 testing (including patient’s personal history)several breast cancers or breast and ovarian cancertwo or more ovarian cancers in one familypresence of bilateral cancers of the breast or ovarycancers diagnosed at younger than expected agesmultiple affected relatives, demonstrating an autosomal dominant pattern of inheritancepresence of individuals diagnosed with more than one cancer, e.g. breast and ovarianbreast and/or ovarian cancer and Ashkenazi (Eastern European) Jewish heritagemale breast cancer
32Cindy’s Story Alice D. 50 ? stomach X 3 No CA Bessie D.91 Br Dx 91 ? Renee65 yoOv dx 46Br dx 52Kate61 yoJohn66 yoJanice61 yoCindy34 yo+ BRCA2mutationJason31 yoJane28 yoRickColon dx 31D. 33Susan30 yoJames5 yoKatherine3 yoJohn Jr.6 yoCaroline2 yoFCRS
33Cindy’s Risk Assessment Gail ModelRace - CaucasianAge - 34Age Menarche - 13Age 1st live birth - 28# Mother, Sister, Daughter with Breast Cancer - 1# previous biopsy - 05 year risk = 0.5% lifetime risk = 19.2%Claus ModelUsing Table of One First Degree RelativePredicted cumulative probability of breast cancer by age:39 = .8%49 = 2.3%59 = 4.9%69 = 8.2%79 = 11%Benichou J, Gail M, Mulvihill J JCO 14:103-10Claus EB, Risch N, Thompson WD, CANCER 73:FCRS
34Hereditary Breast/Ovarian Cancer Syndrome Br ca 44Ov ca 52d. 79d. Br ca 42d. 94 ht dzL br ca 42R br ca 55Oophorectomy (BSO) 53+ BRCA2370-80No cancer753+BRCA2Bil mastectomyBil Salingo-oophorectomy365330-50No cancer52FCRS
35- Risk Perception - Everyone’s is Unique Individual’s view of “high risk”, “common”, “rare”, “unlikely” is colored by their experience and psychological make-up.Half-full vs. half-emptyExperience with statistics (“I will be the <1% who develops ….”)Personal experience with cancer or cancer scares, caring for others with cancer (especially if repeatedly or recently)Relationships and age influence reaction - parent’s cancer and child or adolescent vs. adult, siblings with cancer, friends with cancer.Page DL, Caro SW, Dupont SD, 1998.
36Testing Process Counsel/Education Gather pedigree and documentation Test affected individual for mutationIf family + for mutation, then can test unaffected individualsIf + mutation in family, - mutation in individual, individual risk is close to population riskIf no identified mutation in family, risk is estimated based on history and empiric data
37Outcome of process Clarify risks of cancer Identify individuals who may not be aware of increased riskIdentify individuals who may not be at increased riskIdentify those appropriate for increased cancer surveillance, or measures to decrease risk (prophylactic surgery, chemoprevention), or those appropriate for research on surveillance or chemoprevention
38Options for Women at Risk Increased SurveillanceRisk-reducing SurgeryMedical InterventionFCRS
39Increased Surveillance Breast CancerClinical examination every 6 monthsMammogram yearly beginning age 25-35MRI (ACS 2007)Monthly BSEPrompt evaluation of abnormal findingsOvarian CancerCa-125Pelvic color-doppler ultrasound every 6-12 monthsPelvic examination every 6-12 months
40ACS Recommendations for Breast MRI Screening as an Adjunct to Mammography 2007 Recommend Annual MRI Screening (Based on Evidence*) BRCA mutation First-degree relative of BRCA carrier, but untested Lifetime risk 20–25% or greater, as defined by BRCAPRO or other models that are largely dependent on family historyRecommend Annual MRI Screening (Based on Expert Consensus Opinion ) Radiation to chest between age 10 and 30 years Li-Fraumeni syndrome and first-degree relatives Cowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relativesInsufficient Evidence to Recommend for or Against MRI Screening Lifetime risk 15–20%, as defined by BRCAPRO or other models that are largely dependent on family history Lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) Atypical ductal hyperplasia (ADH) Heterogeneously or extremely dense breast on mammography Women with a personal history of breast cancer, including ductal carcinoma in situ (DCIS)Recommend Against MRI Screening (Based on Expert Consensus Opinion) Women at <15% lifetime risk* Evidence from nonrandomized screening trials and observational studies.Based on evidence of lifetime risk for breast cancer.Payment should not be a barrier. Screening decisions should be made on a case-by-case basis, as there may be particular factors to support MRI. More data on these groups is expected to be published soon.CA Cancer J Clin 2007; 57:75-89
41Risk-Reducing Surgery OophorectomyUnfortunately not 100% effective in eliminating ovarian cancer risk, as intraabdominal carcinomatosis has occurred (2-4%)Questions - hysterectomy?HRT?, do we screen after BSOBilateral oophorectomy reduced risk of breast cancer in BRCA1 mutation carriers. (RR=0.53). HRT did not negate reduction in risk.MastectomyTotal mastectomy vs.. subcutaneous mastectomy?Not 100% effective, true risk reduction unclear, >90%.Hugely personal decisions.Rebbeck TR, Levin AM, Eisen A, et al. JNCI 91(17):1475, Stuewing JP, Watson P, Easton DF, et al JNCI Monographs :330; Eisen A, Rebbeck TR, Wood WC,Weber BL. JCO 18(9)”1980; May Hartmann LC, Daniel JS, Woods JE, et al. NEJM 340(2):77-84, Jan 14, 1999;
42Medical Interventions Ovarian CancerOral contraceptives have been shown to decrease the risk of ovarian cancer in the general population.In women with mutations in BRCA1 or BRCA2 that risk reduction was also documented, with 60% reduction (RR=0.4) with use of 6 years or more.Breast CancerRisk reducing medications should be discussed based on current understanding.Narod SA, Risch H, Moslehi R, et al. NEJM 1998, Aug 13;339(7):Fisher B, Costantino JP, Wickerman DL, et al. JNCI, 1998; 90(18):
43Misconceptions about genetic testing: Testing is not covered by insurance. In most instances insurance covers the cost of testing like any other medical expense.Testing is complicated. True and false – choosing the appropriate test is not always simple, there are significant opportunities for misinterpretation. Seek consultation with a health care provider (nurse practitioner, genetic counselor, MD) specializing in hereditary cancer.Testing will cause you to lose your insurance. Concerns exist about genetic discrimination, but after nearly 15 years of clinical testing, no significant problems have been seen. Members of group health insurance plans have protection under Federal Law (HIPPA, 1996). GINA signed into law May 2008, extends protections from discrimination based on genetic information to those with private health insurance
44“Walking with the Ghosts of My Grandmothers” a painting by Hollis Sigler on the cover of the journal Science October, 1994
45Hereditary Diffuse Gastric Cancer Syndrome Autosomal dominant inheritanceGermline mutations in CDH1/E-Cadherin Gene (described in hereditary gastric families in 1998)Initially found in Maori families, since described in families from many ethnic groups.Penetrance thought to be 70%,Also increased risk of colon cancer and breast cancer
46Cowden syndromeAn autosomal dominantly inherited hamartoma syndrome with an incidence ofat least 1/200,000 (probably an underestimate)(hamartomas are benign, disorganized growths)characterized by multiple hamartomas that can occurin any organ of the bodypathognomonic cutaneous feature is the trichilemmoma,a benign tumor derived from outer-root sheath epithelium of a hair follicleCarries a high risk of breast, thyroid, and endometrial cancersVariable expressionHighly penetrant:Usually presents by the late teens to the late 20’s90% of individuals with CS have symptoms by age 20By the 3rd decade, 99% of affected individuals wouldhave developed mucocutaneous lesionsAge-dependent penetrance: only 10% exhibit symptoms by age 10
47Cowden syndromeAssociated with inherited alterations in the gene, PTEN(‘phosphatase and tensin homolog deleted on chromosome ten’),also sometimes called MMAC1 (‘mutated in multiple advanced cancer’) which was isolated in 1997PTEN is located on chromosome 10q23Function of PTEN:Tumor suppressorControls pathway for regulation of cell proliferation andcell survivalAlterations in PTEN also associated withBannayan-Riley-Ruvalcaba (BRR) syndrome and a small percentageof cases of juvenile polyposis syndrome (JPS).
48Cancer Risks Associated with Cowden Syndrome: Female Breast Cancer 25%-50% lifetime risk (vs ~11% in general pop.)Average age of diagnosis may be around age 38-46Thyroid Carcinoma 3%-10% lifetime risk (vs 1% in general population)Non-medullaryUsually follicular, but can be papillaryEndometrial Cancer %Other cancers may be associated with Cowden syndrome:Genitourinary Mucocutaneous Male Breast GastrointestinalCentral Nervous System medulloblastomas are more commonOther, e.g. liposarcoma
49Li-Fraumeni SyndromeInitially described by Frederick Li and Joseph Fraumeni (1969) as syndrome associated with sarcomas and other diverse tumors.Associated cancer include soft-tissue sarcoma, osteosarcoma, early-onset breast cancer, brain tumors, adrenocortical carcinoma, and leukemias, primarily acute leukemia. (Was also called SBLA for Sarcoma, Breast/Brain, Leukemia, and Adrenal)Inherited in an autosomal dominant manner.Other reports have associated other cancers - including melanoma, cancers of the stomach, pancreas, colon, and esophagus, and gonadal germ cell tumors.Gene mutations TP53 (1990) on 17p13, possibly others
50DNA BANKINGIf genetic testing is not possible or not informative, DNA banking is a relatively inexpensive and simple procedure that can save a sample of the affected person’s DNA for future testing.
51Resources to find cancer genetics professionals in your area: genetests.org
55Selected Hereditary Cancer Syndromes Hereditary Breast/ovarian cancerBRCA1, BRCA2, CHEK2 Other?Breast, ovarian prostate, pancreatic r (BRCA2), ? Colon and other cancersSite specific breast cancerBRCA1, BRCA2BreastSite specific ovarian cancerOvarianLi-Fraumeni SyndromeTP53, CHEK2Breast, sarcomas, adrenocortical carcinoma, leukemia, brain tumorsCowdenPTENBreast, thyroid, benign lesions of skin, breast, thyroid; renal cell carcinomaPeutz-Jegher SyndromeSTK11Breast cancer, benign ovarian tumors, testicular tumors, pancreatic cancer, polyps (ureter, bladder, GI tract, renal pelvis, characteristic skin lesions (melanin spots, lips, buccal mucosaFamilial adenomatous polyposisAPC, MYHPolyposis, colorectal cancer, thyroid gastric cancer, periampullary carcinoma, hepatoblastomaVariant of FAP - Attenuated FAPAPC<100 colorectal polyps, later age onset CRC, gastric, duodenal adenomas or cancerVariant of FAP - Gardner’s SyndromeOsteomas of skull and mandible, CHRPE, dental anomalies, lymphangiomas, lipomas, desmoidsHNPCC (Lynch Syndrome)MLH1, MSH2, MSH6, PMS1, PMS2,Colorectal cancer (often right sided and multifocal), endometrial ca, ovarian ca, small bowel, stomach, pancreas, ureter, renal pelvisTurcot’s SyndromeAPC, MMR genesColorectal adenomas, CRC, primary brain tumors (mudulloblastoma APC, glioblastoma MMR)OMIM, Elsas LJ, Trepanier A. Cancer Genetics in Primary Care. Postgraduate Medicine 107(4): , April 2000., Offit K. Clinical Cancer Genetics, Wiley-Liss, 1998, New York.
56Selected Hereditary Cancer Syndromes (cont’d) MENMEN1, RETMultiple endocrine cancersRetinoblastomaRB1Retinoblastoma, often bilateral and < 1 year of age, also associated increased risk of sarcoma, melanoma, brain tumorsVon Hippel-LindauVHLRenal cell carcinoma, retinal angioma, cerebellar hemangioblastoma, pheochromocytoma, pancreatic cysts, islet cell tumorProstate cancerHPC1, BRCA1, p53Earlier age onset prostate cancer, maybe part of other syndromesPancreatic cancerBRCA2, MADH4, TP53, CDKN2A, ARMET, +++Other syndromes, HNPCC, HBOC, Li-Fraumeni, VHL, melanoma, hereditary pancreatitis, site specific pancreatic caMelanomaP16, CDK4, othersMelanoma, dysplastic nevi, pancreatic caOMIM, Elsas LJ, Trepanier A. Cancer Genetics in Primary Care. Postgraduate Medicine 107(4): , April 2000., Offit K. Clinical Cancer Genetics, Wiley-Liss, 1998, New York
57Stigmata of Selected Syndromes Associated with Susceptibility to Cancer Syndrome Major Cancer Risks Selected physical findingsCowden SyndromeBreast cancerFacial papules, oral “cobblestone” papules, macrocephalyDown SyndromeAcute leukemiaCharacteristic facies, round head, congenital heart diseaseFancomi AnemiaUpper extremity malformations, increased skin pigmentationFAP (Gardner’s subtype)Colon cancerRetinal pigmentation, sebaceous cysts, osteomas, impacted teeth, exostoses, , desmoids, florid polyposisMuir-Torre syndromeColon cancer, skin tumorsSebaceous adenomata, keratocanthomata, basal cell carinomas,Multiple Endocrine Neoplasia type 2bMedullary thyroid carcinoma, pheochromocytoma,Enlarged and nodular lips, Marfanoid habitusPeutz-Jegher syndromeBreast, colon cancersDark spots on lips, perioral areas, buccal mucosa and extremetiesTurcot syndromeColon cancer, brain tumorsPolyps, café-au-lait spots, sebaceous cysts on skin“WAGR” syndrome (Wilm’s tumor, aniridia, genitourinary abnormalities and mental retardation)Wilm’s tumorAniridia, genitourinary malformationsOffit, K. Clinical Cancer Genetics, Risk Counseling & Management, Wiley-Liss, New York, 1998.
58RED FLAGS – Think about hereditary susceptibility when you see: Breast Cancer at age less than 50Ashkenazi Jewish heritage and breast or ovarianMore than one ovarian cancer in a family, or breast and ovarian cancerMen with breast cancerMore than one pancreatic cancer in a familyColorectal cancer less than 50 years of agePolyposisPheochromocytomaMedullary thyroid cancer