All in the Family: Using Family HealthHistory to Identify and Support Women at Risk             for Hereditary Cancer     ...
Objectives1. Understand the genetic consultation process2. Examine genetic contribution to breast   cancer3. Identify sugg...
Reasons for a Genetics Consultation1. Family history of a medical condition       •   Cancer, heart disease, Huntington di...
NorthShore Clinical Genetics Practice• Busiest adult genetic clinic in Midwest   – Vying for busiest in US• Patient visits...
The Consultation AppointmentWhat occurs at an initial genetics consultation?  – Meet with a genetic counselor and a geneti...
Genetic Counseling Process• Using a questionnaire as a guide, the patient gathers  detailed information on their personal/...
Genetic Counseling Process – Information Gathering
Costs of genetic testing• Genetic counseling and genetic testing fees are separate   – Both are usually covered• About 95%...
Genetic Information Non-discrimination Act (GINA)   • Federal law signed into law May 21st, 2008      – Went into effect i...
Facilitate Decision-makingNot a simple decision …  – Should I have testing?  – What would I do differently if I    were to...
Genetic Counseling Process – Disclosing Results The disclosure appointment:    –   Scheduled based on anticipated time of ...
About 5-10% of breast and ovarian cancer is hereditary—       caused by single, strong, dominant genes
BRCA1/2 contribution to breast cancer …• Woman with breast cancer - ~5%  – Of Ashkenazi Jewish ancestry - ~10%• Diagnosed ...
Frequency of BRCA1 & BRCA2 mutations General population              Ashkenazi Jewish                                     ...
Clinical Case• 53 year old woman diagnosed with breast cancer• Underwent bilateral mastectomy with  reconstruction, chemot...
Significant family history of breast cancer:    • Mother BC age 40    • 4 paternal relatives with BC    • Young-onset BC (...
Risk assessment and genetic testing• Her motivations for genetic testing:  – determine her risk of ovarian cancer  – „put ...
Use the right model to get the right answerModified From: Rubinstein WS, O‟Neill SM: Quantitative Risk Assessment. In: Sin...
Levels of BRCA1 and BRCA2 testing• Multi-site analysis   – AJ Founder mutations – 80-90%   – BRCA1 187delAG and 5385insC  ...
Costs of genetic consultation and testing• Genetic counseling and genetic testing fees are separate   – Both are usually c...
Risk assessment and genetic testing• Her motivations for genetic testing:   – determine her risk of ovarian cancer   – „pu...
BRCA1 and BRCA2 lifetime cancer risks       Breast cancer (+ early age at onset)       (50-85%)       Second primary breas...
Cancer screening and prevention:                 the patient• Evidence-based medicine    – ovarian cancer lifetime risk 20...
In genetics, the family is the patient
In genetics, the family is the patient
Genetic testing, cancer screening   and prevention: the sister• Sister underwent genetic testing,  also a BRCA2 886delGT m...
“I’d have been here sooner if it hadn’t been for early detection.”
BRCA1 and BRCA2 lifetime cancer risks       Breast cancer (+ early age at onset)       (50-85%)       Second primary breas...
Cancer Risk Management in BRCA1/2 carriersBreast cancer – Screening• Annual mammography/MRI start age 20-25• Clinical brea...
Other Cancers with BRCA1/2•   Male Breast•   Prostate•   Pancreatic•   Stomach•   Melanoma of the skin and eye•   Colon ca...
Recognition ofHereditary Cancer Syndromes
When to SuspectHereditary Cancer Syndrome• Cancer in 2 or more close relatives  (on same side of family)• Early age at dia...
Most Cancer Susceptibility Genes are Dominant with Incomplete Penetrance                                                  ...
Features of hereditary breast-ovarian          cancer (BRCA1 and BRCA2)•   Early age of breast cancer onset•   Ovarian can...
―Family History is Negative             for Breast Cancer‖Need more information to pick the right gene• Ovarian cancer, ma...
Li-Fraumeni syndrome•   Young breast cancer (most common cancer)•   Adrenocortical carcinoma•   Sarcoma•   Leukemia
J Clin Oncol 27:1250-1256.
Pathognomonic mucocutaneous features of          Cowden syndrome                               (a) Trichilemmomas on the  ...
What if genetic testing in a family with significant        breast cancer history is negative?   • BRCA1/2 testing ~90%   ...
Breast MRI Surveillance• Higher sensitivity for  detection of invasive  breast cancers• Mammography has  higher sensitivit...
Who is considered high risk?
ACS Recommendations for Breast MRIScreening as an Adjunct to Mammography               Saslow D et al. (2007) CA Cancer J ...
Continue to follow-up …• Family history changes   – New information   – New cancer diagnosed in family (missed 10%     fam...
NorthShore Center for Medical Genetics                 Clinical ResearchPROSE Study of BRCA1 and BRCA2 Mutation Carriers  ...
The Center for Medical Genetics                    NorthShore University HealthSystem•   Peter Hulick, MD, MMSc        Med...
All in the Family: Using Family Health History to Identify and Support Women at Risk for Hereditary Cancer
All in the Family: Using Family Health History to Identify and Support Women at Risk for Hereditary Cancer
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All in the Family: Using Family Health History to Identify and Support Women at Risk for Hereditary Cancer

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Presentation from Peter Hulick, MD, MMSc, to help nurses and nurse practitioners:
1) Understand the genetic consultation process
2) Examine genetic contribution to breast cancer
3) Identify suggestive family history patterns and risk estimation
4) Influence of genetic testing on management

Taken from a CNE-granting presentation given on 2/17/12 in Highland Park, IL, put together by the Chicago Center for Jewish Genetic Disorders and NorthShore University HealthSystem.

Published in: Health & Medicine, Technology
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All in the Family: Using Family Health History to Identify and Support Women at Risk for Hereditary Cancer

  1. 1. All in the Family: Using Family HealthHistory to Identify and Support Women at Risk for Hereditary Cancer 2/15/12 Peter Hulick, MD MMSc Center for Medical Genetics NorthShore University HeathSystem
  2. 2. Objectives1. Understand the genetic consultation process2. Examine genetic contribution to breast cancer3. Identify suggestive family history patterns and risk estimation4. Influence of genetic testing on management
  3. 3. Reasons for a Genetics Consultation1. Family history of a medical condition • Cancer, heart disease, Huntington disease, connective tissue disease, hearing/visual disorder2. At risk for a hereditary disorder • Thalassemia, Tay-Sachs disease3. Unusual presentation or history • Unexplained/early cardiomyopathy, early onset of cancer4. Exploring recurrence risks for future pregnancies5. Diagnostic evaluation for known syndromes • Klinefelter, Down syndrome
  4. 4. NorthShore Clinical Genetics Practice• Busiest adult genetic clinic in Midwest – Vying for busiest in US• Patient visits FY2011 – 658 New – 1134 Total• Focus – Hereditary cancer – Breadth of adult genetics diagnoses – Expanding to pediatrics and more non-cancer
  5. 5. The Consultation AppointmentWhat occurs at an initial genetics consultation? – Meet with a genetic counselor and a geneticist – Personal and family medical history reviewed – Targeted physical exam when appropriate – Discussion of genetic concepts, risks, and testing options – Patient has option to decline or proceed with genetics testing if indicated – Disclosure appointment scheduled if decision to test – Typical initial appointment lasts 1.5 hours
  6. 6. Genetic Counseling Process• Using a questionnaire as a guide, the patient gathers detailed information on their personal/family history – Current ages – Ages at death – Causes of death – Site that cancer originated? (i.e. uterine vs ovarian cancer?) – Other questions, depending on reason for referral » Who has had colonoscopies? » Number and type of polyps on colonoscopy? » Have the women had hysterectomies? » Skin biopsies –what was found?
  7. 7. Genetic Counseling Process – Information Gathering
  8. 8. Costs of genetic testing• Genetic counseling and genetic testing fees are separate – Both are usually covered• About 95% of patients use their insurance for consultation and genetic testing – Coverage is typically 70-100% – Medicare often covers consultation and genetic testing fees
  9. 9. Genetic Information Non-discrimination Act (GINA) • Federal law signed into law May 21st, 2008 – Went into effect in May/Nov of 2009 • Prohibits genetic discrimination by health insurance companies and employers • Defines genetic information as predictive genetic tests, family members‟ genetic tests, and family history information • Applies to both group and individual health insurance markets • Prohibits the use of genetic information in underwriting • Prohibits insurers and employers from requiring genetic testing
  10. 10. Facilitate Decision-makingNot a simple decision … – Should I have testing? – What would I do differently if I were to test positive? – Will it help my family members? – Now that I have tested positive, should I do high risk screening or do I go onto preventative surgery? – Is a negative test a true negative?
  11. 11. Genetic Counseling Process – Disclosing Results The disclosure appointment: – Scheduled based on anticipated time of results » BRCA1/2 testing 2-3 weeks » LQT syndrome 2-3 months – Everyone scheduled for a return disclosure appt. » Patient not “positive” just because they are returning » Risk implications/adjustments in setting of negative test » Recommendations for treatment/screening » Emotional support » Assistance with appropriate referrals » Implications for family members – duty to warn
  12. 12. About 5-10% of breast and ovarian cancer is hereditary— caused by single, strong, dominant genes
  13. 13. BRCA1/2 contribution to breast cancer …• Woman with breast cancer - ~5% – Of Ashkenazi Jewish ancestry - ~10%• Diagnosed w/ breast cancer <45 yrs - ~ 10% – >45 yrs - ~2% – < 45 yrs and AJ - ~26%• Woman and FHx Br Ca <45 - ~20% – Of AJ ancestry – ~30% Cancer Res 2006; 66(16): 8297-308
  14. 14. Frequency of BRCA1 & BRCA2 mutations General population Ashkenazi Jewish 3 Founder Mutations BRCA1 187delAG 5382insC BRCA2 1 in 300 1 in 40 6174delT
  15. 15. Clinical Case• 53 year old woman diagnosed with breast cancer• Underwent bilateral mastectomy with reconstruction, chemotherapy, hormonal therapy• Eager to get back to work so that she could focus on matters other than her health• Significant family history of breast cancer• Surgeon told her about the link between breast and ovarian cancer and referred her for genetics consultation
  16. 16. Significant family history of breast cancer: • Mother BC age 40 • 4 paternal relatives with BC • Young-onset BC (35) in cousin, linked through father w/ colon & prostate CA
  17. 17. Risk assessment and genetic testing• Her motivations for genetic testing: – determine her risk of ovarian cancer – „put all this behind her‟ – clarify her sister‟s risk of breast cancer• Calculated 43% chance of having a positive gene test (i.e. a mutation)
  18. 18. Use the right model to get the right answerModified From: Rubinstein WS, O‟Neill SM: Quantitative Risk Assessment. In: Singletary SE, Robb GL, Hortobagyi GN (eds):Advanced Therapy of Breast Disease, Second Edition. BC Decker, Inc., 2nd Edition, pp. 97-112, 2004.
  19. 19. Levels of BRCA1 and BRCA2 testing• Multi-site analysis – AJ Founder mutations – 80-90% – BRCA1 187delAG and 5385insC – BRCA2 6174delT• Comprehensive – “spell-check” of the genes – sequencing – 5-site rearrangement panel of BRCA1• BART – Rearrangements in BRCA1 and 2 – Adds 1-3% detection in high risk families
  20. 20. Costs of genetic consultation and testing• Genetic counseling and genetic testing fees are separate – Both are usually covered• Genetic testing – ~$400 to ~$3000 » Lower costs apply when familial mutation is known – We help patients obtain preauthorization and write letters of medical necessity• ~95% of patients use their insurance for consultation and genetic testing » Coverage is typically 70-100% » Medicare often covers consultation and genetic testing fees
  21. 21. Risk assessment and genetic testing• Her motivations for genetic testing: – determine her risk of ovarian cancer – „put all this behind her‟ – clarify her sister‟s risk of breast cancer• Calculated 43% chance of having a positive gene test (i.e. a mutation)• Testing covered by insurance – she said she would get testing regardless of coverage• Results: BRCA2 886delGT mutation
  22. 22. BRCA1 and BRCA2 lifetime cancer risks Breast cancer (+ early age at onset) (50-85%) Second primary breast cancer (40-60%) Male breast cancer (5-6%) Prostate cancer Ovarian cancer (30-40%) (20%-40%) Increased risk of pancreatic, fallopian tube, other cancers
  23. 23. Cancer screening and prevention: the patient• Evidence-based medicine – ovarian cancer lifetime risk 20-40% – preventive removal of ovaries and fallopian tubes reduces ovarian cancer risk by 96%• Patient referred by geneticist to gynecologic oncologist• Laparoscopic removal of ovaries and fallopian tubes shortly after finishing chemotherapy for breast cancer• Pathology revealed ovarian cancer – stage 1-C: caught very early, 90% cure rate – underwent 6 cycles of chemotherapy• Patient remains free of evident disease and is probably cured – “natural presentation” is late-stage with poor survival rates
  24. 24. In genetics, the family is the patient
  25. 25. In genetics, the family is the patient
  26. 26. Genetic testing, cancer screening and prevention: the sister• Sister underwent genetic testing, also a BRCA2 886delGT mutation carrier• Breast and ovarian cancer screening was negative• Underwent preventive removal of ovaries and fallopian tubes and prophylactic mastectomy• Stage 1 breast cancer diagnosed
  27. 27. “I’d have been here sooner if it hadn’t been for early detection.”
  28. 28. BRCA1 and BRCA2 lifetime cancer risks Breast cancer (+ early age at onset) (50-85%) Second primary breast cancer (40-60%) Male breast cancer (5-6%) Prostate cancer Ovarian cancer (30-40%) (20%-40%) Increased risk of pancreatic, fallopian tube, other cancers
  29. 29. Cancer Risk Management in BRCA1/2 carriersBreast cancer – Screening• Annual mammography/MRI start age 20-25• Clinical breast exam every 6 months• Monthly self breast examBreast cancer – Prevention• Tamoxifen chemoprevention (50% effective)• Prophylactic mastectomy (90-95% effective)• Prophylactic oophorectomy (40% effective against breast cancer)Ovarian cancer – Screening• Transvaginal ultrasound + Ca-125 every 6-12 months limited efficacyOvarian cancer – Prevention• PBSO after childbearing complete (80-96% effective) strongly recommended• Consider oral contraceptives
  30. 30. Other Cancers with BRCA1/2• Male Breast• Prostate• Pancreatic• Stomach• Melanoma of the skin and eye• Colon cancer: inconsistently observed
  31. 31. Recognition ofHereditary Cancer Syndromes
  32. 32. When to SuspectHereditary Cancer Syndrome• Cancer in 2 or more close relatives (on same side of family)• Early age at diagnosis• Multiple primary tumors• Bilateral or multiple rare cancers• Constellation of tumors c/w specific cancer syndrome breast + ovary = HBOC colon + endometrial = HNPCC colon + adenomatous polyposis = FAP melanoma + pancreatic = p16• Evidence of autosomal dominant transmission
  33. 33. Most Cancer Susceptibility Genes are Dominant with Incomplete Penetrance Normal Susceptible Carrier Carrier, affected with cancer Sporadic cancer• Penetrance is often incomplete• May appear to “skip” generations• Individuals inherit altered cancer susceptibility gene, not cancer• Paternal family history matters!
  34. 34. Features of hereditary breast-ovarian cancer (BRCA1 and BRCA2)• Early age of breast cancer onset• Ovarian cancer at any age• Bilateral breast cancer, or more than once• An individual with both ovarian and breast cancer• Many relatives affected; multiple generations• Male breast cancer• Other cancers in the family, e.g. pancreas• Ashkenazi Jewish ancestry• Medullary breast cancer (BRCA1)• ER/PR/Her2 neg (triple negative) breast cancer (BRCA1)
  35. 35. ―Family History is Negative for Breast Cancer‖Need more information to pick the right gene• Ovarian cancer, male breast cancer, pancreatic, prostate cancer: BRCA1, BRCA2• Sarcoma, childhood leukemia/lymphoma, others: TP53 (Li-Fraumeni syndrome)• Thyroid, endometrial, trichilemmomas, hamartomas: PTEN (Cowden syndrome)• Diffuse gastric cancer, lobular breast cancer: CDH1 (Hereditary diffuse gastric cancer)• Ovarian (granulosa), testicular, pancreatic, uterine, GI; intestinal hamartomatous polyps, mucocutaneous pigmentation: STK11 (Peutz-Jeghers)
  36. 36. Li-Fraumeni syndrome• Young breast cancer (most common cancer)• Adrenocortical carcinoma• Sarcoma• Leukemia
  37. 37. J Clin Oncol 27:1250-1256.
  38. 38. Pathognomonic mucocutaneous features of Cowden syndrome (a) Trichilemmomas on the nape of the neck (b) Palmar keratoses (c) Perioral papillomatous papules (arrow head) and nasal polyposis (d) Gastric hamartomas as seen by endoscopy European Journal of Human Genetics (2008) 16, 1289–1300
  39. 39. What if genetic testing in a family with significant breast cancer history is negative? • BRCA1/2 testing ~90% sensitive • Risk models for lifetime risk calculation – Tyrer-Cusick – Gail • Addition of MRIs? • Tamoxifen?
  40. 40. Breast MRI Surveillance• Higher sensitivity for detection of invasive breast cancers• Mammography has higher sensitivity for ductal carcinoma in situ (DCIS)• Reserved for screening high risk patients
  41. 41. Who is considered high risk?
  42. 42. ACS Recommendations for Breast MRIScreening as an Adjunct to Mammography Saslow D et al. (2007) CA Cancer J Clin 2007; 57:75-89
  43. 43. Continue to follow-up …• Family history changes – New information – New cancer diagnosed in family (missed 10% families, different syndrome to consider?)• Genetic testing – BART relatively recent – New gene(s) clinically available for testing• New Screening guidelines – MRI for women with 20-25% lifetime risk of developing breast cancer
  44. 44. NorthShore Center for Medical Genetics Clinical ResearchPROSE Study of BRCA1 and BRCA2 Mutation Carriers – How do lifestyles, habits, exposures, hormones, preventive surgery and other interacting genes influence cancer risk?Pancreatic Cancer Family Registry (PCFR) – Database for families affected by pancreatic cancer in hopes of learning the causes of familial pancreatic cancerIMPACT Study – Evaluation of usefulness of prostate cancer screening methods for screening high risk BRCA positive menSIFT Registry – Families with history of breast cancer but negative genetic testing for breast cancer susceptibility genes
  45. 45. The Center for Medical Genetics NorthShore University HealthSystem• Peter Hulick, MD, MMSc Medical Geneticist• Genetic Counselors Scott Weissman, MS, CGC Anna Newlin, MS, CGC Kristen Vogel, MS, CGC Shelly Weiss, MS, CGC• Research Coordinator Tina Selkirk, MS
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