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Who should be screened for hereditary breast and ovarian cancer

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Slide 1 - Hereditary breast and ovarian cancerWho should be screened and How? Symposium on Cancer Waterloo Inn October 31, 2007 Mala Bahl, MD, MSc
Slide 2 - Objectives Describe genetic syndromes associated with breast and ovarian cancers Identify those at high risk for hereditary breast or ovarian cancer Review cancer screening and risk reduction measures relative to the general population Review referral opportunities for such patients
Slide 3 - This presentation contains no conflicts of interest
Slide 4 - General population risk Breast cancer 10.6% 1 in 9 women Ovarian Cancer 1.5% 1 in 70 women
Slide 5 - Breast Cancer Risk Factors Familial/genetic 1st degree relatives at 1.5-3 x risk Age Reproductive/hormonal Lifestyle Environmental Previous breast disease The majority of cases have no identifiable risk factor!
Slide 6 - Contribution of Family History 15-20% have an affected 1st/2nd degree relative ~5% -Family history suggests high-risk gene mutation Majority are “sporadic” 5-10% ~15-20%
Slide 7 - Two hit hypothesis ? age 30-50 ?age 50-70
Slide 8 - Two hit hypothesis ? age 30-50 ?age 50-70
Slide 9 - Familial Vs Hereditary Familial Clustering 2  cases in a family Not necessarily young cases (cases >60 years) Not necessarily related cancers No clear pattern seen Shared genetics Shared environment Shared lifestyle Chance
Slide 10 - Jean Cervical 39 Fred 41 Susan 37 Lori 33 Michael 30 John 65 Mary Breast 60 Charles 74 Prostate 68 Louise d.62 Colon 59 Agnes Breast 76 Familial Cancer
Slide 11 - Familial Vs Hereditary Hereditary Multiple generations with same cancer Early onset >1 cancer / individual especially in paired organs Pattern fits with known cancer syndrome Presence of rare cancers Most are autosomal dominant with incomplete penetrance (like BRCA1 and 2!)
Slide 12 - Hereditary Ovary, 40 Breast, 45 Colon, 67 Breast,50 Ovary 50 Breast, 35
Slide 13 - Factors that Influence Phenotype Penetrance Gender Co-morbidites Lifestyle Environment Modifier genes Risk-Reduction
Slide 14 - ASCO Causes of Hereditary Breast Cancer Gene BRCA1 BRCA2 TP53 Li-Fraumenni PTEN Cowden’s CHEK2 Undiscovered genes % of Hereditary Breast Cancer 20%–40% 10%–30% <1% <1% <1% 30%–70% BOCS
Slide 15 - Breast and Ovarian Cancer Syndrome Refers to BRCA1 or BRCA2 AD inheritance Tumor Suppressors- a caretaker function 1 in 800 women in the general population BRCA1 identified in 1994 >600 mutations BRCA2 in 1995 ~ 450 mutations
Slide 16 - Founder mutations 4 founder mutations among Ashkenazi Jews Prevalence 1 in 40 Other groups with BRCA!/2 mutation families French-Canadian Mennonite Icelandic Scandinavian Irish British Dutch Japanese Pakistani
Slide 17 - Hereditary Breast and Ovarian Cancer: BRCA1 Breast ca risk by age 50: 50% Risk for Male Breast Cancer Unclear Risk for Prostate Cancer if < 65 Breast cancer 85% Second primary breast cancer 40%-60% Ovarian cancer 20%-40% Adapted from ASCO
Slide 18 - Hereditary Breast and Ovarian Cancer: BRCA2 prostate cancer(12-18%) melanoma (2.5x) bile duct (5x), pancreas ca (~5%) breast cancer (30%-85%) ovarian cancer (10%-20%) male breast cancer (6.7%) Adapted from ASCO
Slide 19 - Clues to Breast/Ovarian Ca Syndrome Breast Cancer < age 35  2 cases Breast ca before age 50 Bilateral breast cancer, first <50 Serous ovarian cancer Breast and ovarian cancer in the same woman Male breast cancer Ashkenazi Jewish heritage with breast cancer ASCO
Slide 20 - More Breast Cancer Syndromes (<1%) Cowden’s – 25-50% breast ca risk Oral lesions, GI hamartomas, benign breast dz Thyroid, uterine lesions or CA, macrocephaly Li-Fraumeni – breast ca < age 40 Often childhood cancers sarcoma, leukemia, brain adrenocortical CA Peutz-Jeghers - <1% Childhood GI hamartomas, colon CA Pigmentation of lips, buccal mucosa, hands/feet
Slide 21 - Clinical Management Options Screening and other interventions
Slide 22 - Who needs what? Family History Assessment Personalized prevention recommendations Referral for genetic evaluation Standard prevention recommendations Intervention Average Moderate (“Familial”) High (Genetic) Risk
Slide 23 - Ontario Screening Guidelinesfor the general population Breast Mammogram every 1-2 years from 50 Annual clinical breast exam for all women Monthly breast self exam for all women No guidelines for men Ovary No gen population screening guidelines
Slide 24 - Moderate Risk Families Low risk of BRCA1/ 2 or other cancer syndromes Lifetime risk 10-30% Screening recommendations: BSE monthly; CBE once or twice a year Annual (digital) mammo from 40 or 5-10 yrs prior to youngest cancer Immediate biopsy of any suspicious findings Explore Chemoprevention Lifestyle modifications
Slide 25 - Lifestyle Modification Good for all risk categories! Exercise – 30 min. or more most days Weight control Diet ?? Less saturated/trans fat Less refined flour, sugar More fruits/vegetables, whole grains, legumes Alcohol: less than 1-2 drinks/day Breast feeding
Slide 26 - Options for High Risk Patients Increased surveillance Prophylactic surgery Lifestyle changes Chemo prevention
Slide 27 - Surveillance: BRCA1/2 Breast Annual mammogram from age 30 (digital) Annual Breast MRI from 30 CBE q6-12mos from age 18 Monthly breast self exam from age 18 Ovarian screening – significant limitations Ca-125, TV ultrasound 1-2/yr- age 25-35 Suboptimal early detection high false positive Preferred in a research setting Class I Class B Class E
Slide 28 - Other Heightened male breast screening Chest wall exams, visual Consider PSA at age 40 Monitor skin and general health Pancreatic screening research (BRCA2)
Slide 29 - Challenges to Surveillance CBE detects few cancers missed by above Promotes awareness no  mortality Mammo insensitive in younger patients 26-42% MRI Sensitivity 83-100% Lower specificity TV US +FH, Sensitivity 92%, Specificity 97.8% PPV 11%; if  2 cases, PPV=20% CA 125 Sensitivity 35-55%
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Slide 31 - Series of 3991 high-risk pts 155 cancers 78% of cancers detected by MRI 38% by mammo 18 (10 DCIS, 8 invasive) on mammo NOT MRI 42% by US (<1% detected by US only) Interval cancer < 10% if MRI Of MRI detected cancers 12-27% DCIS if invasive ca 75-94% < 2 cm Axillary node mets seen in 17-25%
Slide 32 - Other Management Options BRCA1/2 Mastectomy Cohort shows 96% breast ca Total Mastectomy, no node dissection Path review- cancer found in 7% Oophorectomy  ovarian ca 85% Breast ca by 50-66% Birth Control Pill Tamoxifen
Slide 33 - Your Role Detailed family history Cancer status in 1st and 2nd degree relatives Type of primary cancer(s) in each relative Age of disease onset Cancer status in both sides of the family Ethnic background on both sides Other medical findings – benign tumors, etc.
Slide 34 - Referral opportunities Referral forms available at our website www.grandriverhospital.on.ca follow links to GRRCC, then Treatments & Services then Genetic Counseling Service
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