Oct. 2013 Via Christi Women's Connection presentation on breast cancer genetic testing featuring Patty Tenofsky, MD, with Via Christi Clinic in Wichita, Kan.

1. Breast cancer genetic testing:
Is it right for you?
Patty Tenofsky, MD FACS
Women‘s Connection
October 8, 2013

2. Angelina Jolie

3. Marcheline Bertrand

4. Angelina Jolie‘s decision
• “The truth is I carry a „faulty‟ gene, BRCA 1,
which sharply increases my risk of
developing breast cancer and ovarian
cancer.”
• Her mother had previously battled breast cancer, but
then developed ovarian cancer at age 49 and died of
the disease at age 56
• Her Grandmother died of ovarian cancer at age 45
• Her maternal aunt died of breast cancer
• She chose to have bilateral preventive double
mastectomies.
• She plans to have her ovaries removed once she has
decided that she does not want any more children.

5. Christina Applegate
• She was diagnosed
with breast cancer,
and then found to
have the BRCA 1
gene at age 36
• She chose to have
bilateral
mastectomies

6. Breast & Ovarian Cancer
• 200,000 cases of Breast Cancer/year in the U.S.
– Lifetime risk is around 10-13%
– Risk factors
• Being a woman and getting older
• Family history, early menarche, late or no
pregnancy, hormone replacement, alcohol use,
obesity, lack of exercise
• 25,000 cases of Ovarian Cancer/year in the U.S.
– Lifetime risk is <2%

7. Most Women Develop Breast Cancer
WITHOUT a Family History

8. Hereditary Breast & Ovarian
Cancer Syndrome (BRCA)
• Characterized by significantly
increased risks for breast and ovarian
cancer
– 1:800 people in the general population
have a BRCA genetic mutation
– 1:40 people of Eastern European Jewish
descent will have the gene.
• Most cases are caused by a BRCA1
or BRCA2 mutation
• Clinical testing is available to identify
individuals with mutations

9. DNA
• Double Helix
• Made up of 4 building blocks
that get together in pairs
– Adenine (A), thymine (T) ,
guanine (G), cytosine (C)
• These 4 ―letters‖ create a
―word‖ that codes for a certain
amino acid. Amino Acids are
the building blocks of our
proteins – these proteins are
what lead to our characteristics
and features
• Misplaced letters or words can
lead to severely incorrect
proteins (mutations)

10. Sickle Cell Anemia – only
one base code incorrect

11. What is the purpose of our
normal BRCA genes?
• BRCA gene‘s purpose: It codes for proteins
that function to fight changes in your DNA that
can lead to breast and ovarian cancer.
– Changes may occur in your DNA which can
lead to cancer when normal cells divide and
are exposed to cancer inducing substances
– BRCA gene is therefore a cancer fighter
• BRCA gene that is mutated: The body is less
able to find and repair mistakes and cancer is
more likely.

12. Background
• 1990 – Families who had many women
with breast and ovarian cancer underwent
DNA studies and scientists identified the
first gene associated with breast cancer:
BRCA 1 on Chromosome 17.
• 1994 – BRCA 2 gene was discovered on
Chromosome 13.
• Jewish families were found to have a
much higher rate of the gene mutations.
• By the late 1990s – we were able to test
for the gene mutations.

13. Human Chromosomes

14. Laboratory Testing for
Genetic Mutations
• BRCA1: > 5,500 bp– AGCTCGCTGAGACTTCCTGGACCCCGCACCAGGCTGTGGGGTTTCTCAGATAACTGGGCCCCTGCGCTCAGGAGGCCTTCACCCTCTGCTCTGGGTAAAGTTCATTGGAACAGAAAGAAATGGATTTATCTGCTCTTCGCGTTGAAGAAGTACAAAATGTCATTAATGCTATGCAGAAAATCTTAGAGTGTCCC
ATCTGTCTGGAGTTGATCAAGGAACCTGTCTCCACAAAGTGTGACCACATATTTTGCAAATTTTGCATGCTGAAACTTCTCAACCAGAAGAAAGGGCCTTCACAGTGTCCTTTATGTAAGAATGATATAACCAAAAGGAGCCTACAAGAAAGTACGAGATTTAGTCAACTTGTTGAAGAGCTATTGAAAATCATTTG
TGCTTTTCAGCTTGACACAGGTTTGGAGTATGCAAACAGCTATAATTTTGCAAAAAAGGAAAATAACTCTCCTGAACATCTAAAAGATGAAGTTTCTATCATCCAAAGTATGGGCTACAGAAACCGTGCCAAAAGACTTCTACAGAGTGAACCCGAAAATCCTTCCTTGCAGGAAACCAGTCTCAGTGTCCAACTC
TCTAACCTTGGAACTGTGAGAACTCTGAGGACAAAGCAGCGGATACAACCTCAAAAGACGTCTGTCTACATTGAATTGGGATCTGATTCTTCTGAAGATACCGTTAATAAGGCAACTTATTGCAGTGTGGGAGATCAAGAATTGTTACAAATCACCCCTCAAGGAACCAGGGATGAAATCAGTTTGGATTCTGCA
AAAAAGGCTGCTTGTGAATTTTCTGAGACGGATGTAACAAATACTGAACATCATCAACCCAGTAATAATGATTTGAACACCACTGAGAAGCGTGCAGCTGAGAGGCATCCAGAAAAGTATCAGGGTAGTTCTGTTTCAAACTTGCATGTGGAGCCATGTGGCACAAATACTCATGCCAGCTCATTACAGCATGAG
AACAGCAGTTTATTACTCACTAAAGACAGAATGAATGTAGAAAAGGCTGAATTCTGTAATAAAAGCAAACAGCCTGGCTTAGCAAGGAGCCAACATAACAGATGGGCTGGAAGTAAGGAAACATGTAATGATAGGCGGACTCCCAGCACAGAAAAAAAGGTAGATCTGAATGCTGATCCCCTGTGTGAGAGAAAA
GAATGGAATAAGCAGAAACTGCCATGCTCAGAGAATCCTAGAGATACTGAAGATGTTCCTTGGATAACACTAAATAGCAGCATTCAGAAAGTTAATGAGTGGTTTTCCAGAAGTGATGAACTGTTAGGTTCTGATGACTCACATGATGGGGAGTCTGAATCAAATGCCAAAGTAGCTGATGTATTGGACGTTCTA
AATGAGGTAGATGAATATTCTGGTTCTTCAGAGAAAATAGACTTACTGGCCAGTGATCCTCATGAGGCTTTAATATGTAAAAGTGAAAGAGTTCACTCCAAATCAGTAGAGAGTAATATTGAAGACAAAATATTTGGGAAAACCTATCGGAAGAAGGCAAGCCTCCCCAACTTAAGCCATGTAACTGAAAATCTAAT
TATAGGAGCATTTGTTACTGAGCCACAGATAATACAAGAGCGTCCCCTCACAAATAAATTAAAGCGTAAAAGGAGACCTACATCAGGCCTTCATCCTGAGGATTTTATCAAGAAAGCAGATTTGGCAGTTCAAAAGACTCCTGAAATGATAAATCAGGGAACTAACCAAACGGAGCAGAATGGTCAAGTGATGAAT
ATTACTAATAGTGGTCATGAGAATAAAACAAAAGGTGATTCTATTCAGAATGAGAAAAATCCTAACCCAATAGAATCACTCGAAAAAGAATCTGCTTTCAAAACGAAAGCTGAACCTATAAGCAGCAGTATAAGCAATATGGAACTCGAATTAAATATCCACAATTCAAAAGCACCTAAAAAGAATAGGCTGAGGAG
GAAGTCTTCTACCAGGCATATTCATGCGCTTGAACTAGTAGTCAGTAGAAATCTAAGCCCACCTAATTGTACTGAATTGCAAATTGATAGTTGTTCTAGCAGTGAAGAGATAAAGAAAAAAAAGTACAACCAAATGCCAGTCAGGCACAGCAGAAACCTACAACTCATGGAAGGTAAAGAACCTGCAACTGGAGCC
AAGAAGAGTAACAAGCCAAATGAACAGACAAGTAAAAGACATGACAGCGATACTTTCCCAGAGCTGAAGTTAACAAATGCACCTGGTTCTTTTACTAAGTGTTCAAATACCAGTGAACTTAAAGAATTTGTCAATCCTAGCCTTCCAAGAGAAGAAAAAGAAGAGAAACTAGAAACAGTTAAAGTGTCTAATAATGC
TGAAGACCCCAAAGATCTCATGTTAAGTGGAGAAAGGGTTTTGCAAACTGAAAGATCTGTAGAGAGTAGCAGTATTTCATTGGTACCTGGTACTGATTATGGCACTCAGGAAAGTATCTCGTTACTGGAAGTTAGCACTCTAGGGAAGGCAAAAACAGAACCAAATAAATGTGTGAGTCAGTGTGCAGCATTTGA
AAACCCCAAGGGACTAATTCATGGTTGTTCCAAAGATAATAGAAATGACACAGAAGGCTTTAAGTATCCATTGGGACATGAAGTTAACCACAGTCGGGAAACAAGCATAGAAATGGAAGAAAGTGAACTTGATGCTCAGTATTTGCAGAATACATTCAAGGTTTCAAAGCGCCAGTCATTTGCTCCGTTTTCAAAT
CCAGGAAATGCAGAAGAGGAATGTGCAACATTCTCTGCCCACTCTGGGTCCTTAAAGAAACAAAGTCCAAAAGTCACTTTTGAATGTGAACAAAAGGAAGAAAATCAAGGAAAGAATGAGTCTAATATCAAGCCTGTACAGACAGTTAATATCACTGCAGGCTTTCCTGTGGTTGGTCAGAAAGATAAGCCAGTT
GATAATGCCAAATGTAGTATCAAAGGAGGCTCTAGGTTTTGTCTATCATCTCAGTTCAGAGGCAACGAAACTGGACTCATTACTCCAAATAAACATGGACTTTTACAAAACCCATATCGTATACCACCACTTTTTCCCATCAAGTCATTTGTTAAAACTAAATGTAAGAAAAATCTGCTAGAGGAAAACTTTGAGGAA
CATTCAATGTCACCTGAAAGAGAAATGGGAAATGAGAACATTCCAAGTACAGTGAGCACAATTAGCCGTAATAACATTAGAGAAAATGTTTTTAAAGAAGCCAGCTCAAGCAATATTAATGAAGTAGGTTCCAGTACTAATGAAGTGGGCTCCAGTATTAATGAAATAGGTTCCAGTGATGAAAACATTCAAGCAGA
ACTAGGTAGAAACAGAGGGCCAAAATTGAATGCTATGCTTAGATTAGGGGTTTTGCAACCTGAGGTCTATAAACAAAGTCTTCCTGGAAGTAATTGTAAGCATCCTGAAATAAAAAAGCAAGAATATGAAGAAGTAGTTCAGACTGTTAATACAGATTTCTCTCCATATCTGATTTCAGATAACTTAGAACAGCCTA
TGGGAAGTAGTCATGCATCTCAGGTTTGTTCTGAGACACCTGATGACCTGTTAGATGATGGTGAAATAAAGGAAGATACTAGTTTTGCTGAAAATGACATTAAGGAAAGTTCTGCTGTTTTTAGCAAAAGCGTCCAGAAAGGAGAGCTTAGCAGGAGTCCTAGCCCTTTCACCCATACACATTTGGCTCAGGGTT
ACCGAAGAGGGGCCAAGAAATTAGAGTCCTCAGAAGAGAACTTATCTAGTGAGGATGAAGAGCTTCCCTGCTTCCAACACTTGTTATTTGGTAAAGTAAACAATATACCTTCTCAGTCTACTAGGCATAGCACCGTTGCTACCGAGTGTCTGTCTAAGAACACAGAGGAGAATTTATTATCATTGAAGAATAGCTT
AAATGACTGCAGTAACCAGGTAATATTGGCAAAGGCATCTCAGGAACATCACCTTAGTGAGGAAACAAAATGTTCTGCTAGCTTGTTTTCTTCACAGTGCAGTGAATTGGAAGACTTGACTGCAAATACAAACACCCAGGATCCTTTCTTGATTGGTTCTTCCAAACAAATGAGGCATCAGTCTGAAAGCCAGGGA
GTTGGTCTGAGTGACAAGGAATTGGTTTCAGATGATGAAGAAAGAGGAACGGGCTTGGAAGAAAATAATCAAGAAGAGCAAAGCATGGATTCAAACTTAGGTGAAGCAGCATCTGGGTGTGAGAGTGAAACAAGCGTCTCTGAAGACTGCTCAGGGCTATCCTCTCAGAGTGACATTTTAACCACTCAGCAGA
GGGATACCATGCAACATAACCTGATAAAGCTCCAGCAGGAAATGGCTGAACTAGAAGCTGTGTTAGAACAGCATGGGAGCCAGCCTTCTAACAGCTACCCTTCCATCATAAGTGACTCTTCTGCCCTTGAGGACCTGCGAAATCCAGAACAAAGCACATCAGAAAAAGCAGTATTAACTTCACAGAAAAGTAGTG
AATACCCTATAAGCCAGAATCCAGAAGGCCTTTCTGCTGACAAGTTTGAGGTGTCTGCAGATAGTTCTACCAGTAAAAATAAAGAACCAGGAGTGGAAAGGTCATCCCCTTCTAAATGCCCATCATTAGATGATAGGTGGTACATGCACAGTTGCTCTGGGAGTCTTCAGAATAGAAACTACCCATCTCAAGAGG
AGCTCATTAAGGTTGTTGATGTGGAGGAGCAACAGCTGGAAGAGTCTGGGCCACACGATTTGACGGAAACATCTTACTTGCCAAGGCAAGATCTAGAGGGAACCCCTTACCTGGAATCTGGAATCAGCCTCTTCTCTGATGACCCTGAATCTGATCCTTCTGAAGACAGAGCCCCAGAGTCAGCTCGTGTTGG
CAACATACCATCTTCAACCTCTGCATTGAAAGTTCCCCAATTGAAAGTTGCAGAATCTGCCCAGAGTCCAGCTGCTGCTCATACTACTGATACTGCTGGGTATAATGCAATGGAAGAAAGTGTGAGCAGGGAGAAGCCAGAATTGACAGCTTCAACAGAAAGGGTCAACAAAAGAATGTCCATGGTGGTGTCTG
GCCTGACCCCAGAAGAATTTATGCTCGTGTACAAGTTTGCCAGAAAACACCACATCACTTTAACTAATCTAATTACTGAAGAGACTACTCATGTTGTTATGAAAACAGATGCTGAGTTTGTGTGTGAACGGACACTGAAATATTTTCTAGGAATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGGGTGACCCA
GTCTATTAAAGAAAGAAAAATGCTGAATGAGCATGATTTTGAAGTCAGAGGAGATGTGGTCAATGGAAGAAACCACCAAGGTCCAAAGCGAGCAAGAGAATCCCAGGACAGAAAGATCTTCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACATGCCCACAGATCAACTGGAATGGATGGTACAG
CTGTGTGGTGCTTCTGTGGTGAAGGAGCTTTCATCATTCACCCTTGGCACAGGTGTCCACCCAATTGTGGTTGTGCAGCCAGATGCCTGGACAGAGGACAATGGCTTCCATGCAATTGGGCAGATGTGTGAGGCACCTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGTAGCACTCTACCAGTGCCAGGA
GCTGGACACCTACCTGATACCCCAGATCCCCCACAGCCACTACTGACTGCAG
• BRCA2: > 11,000 bp– GGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTGTGGCACTGCTGCGCCTCTGCTGCGCCTCGGGTGTCTTTTGCGGCGGTGGGTCGCCGCCGGGAGAAGCGTGAGGGGACAGATTTGTGACCGGCGCGGTTTTTGTCAGCTTACTCCGGCCAAAAAAGAACTGCACCTCTGGAGCG
GACTTATTTACCAAGCATTGGAGGAATATCGTAGGTAAAAATGCCTATTGGATCCAAAGAGAGGCCAACATTTTTTGAAATTTTTAAGACACGCTGCAACAAAGCAGATTTAGGACCAATAAGTCTTAATTGGTTTGAAGAACTTTCTTCAGAAGCTCCACCCTATAATTCTGAACCTGCAGAAGAATCTGAACATA
AAAACAACAATTACGAACCAAACCTATTTAAAACTCCACAAAGGAAACCATCTTATAATCAGCTGGCTTCAACTCCAATAATATTCAAAGAGCAAGGGCTGACTCTGCCGCTGTACCAATCTCCTGTAAAAGAATTAGATAAATTCAAATTAGACTTAGGAAGGAATGTTCCCAATAGTAGACATAAAAGTCTTCGCA
CAGTGAAAACTAAAATGGATCAAGCAGATGATGTTTCCTGTCCACTTCTAAATTCTTGTCTTAGTGAAAGTCCTGTTGTTCTACAATGTACACATGTAACACCACAAAGAGATAAGTCAGTGGTATGTGGGAGTTTGTTTCATACACCAAAGTTTGTGAAGGGTCGTCAGACACCAAAACATATTTCTGAAAGTCTA
GGAGCTGAGGTGGATCCTGATATGTCTTGGTCAAGTTCTTTAGCTACACCACCCACCCTTAGTTCTACTGTGCTCATAGTCAGAAATGAAGAAGCATCTGAAACTGTATTTCCTCATGATACTACTGCTAATGTGAAAAGCTATTTTTCCAATCATGATGAAAGTCTGAAGAAAAATGATAGATTTATCGCTTCTGT
GACAGACAGTGAAAACACAAATCAAAGAGAAGCTGCAAGTCATGGATTTGGAAAAACATCAGGGAATTCATTTAAAGTAAATAGCTGCAAAGACCACATTGGAAAGTCAATGCCAAATGTCCTAGAAGATGAAGTATATGAAACAGTTGTAGATACCTCTGAAGAAGATAGTTTTTCATTATGTTTTTCTAAATGTA
GAACAAAAAATCTACAAAAAGTAAGAACTAGCAAGACTAGGAAAAAAATTTTCCATGAAGCAAACGCTGATGAATGTGAAAAATCTAAAAACCAAGTGAAAGAAAAATACTCATTTGTATCTGAAGTGGAACCAAATGATACTGATCCATTAGATTCAAATGTAGCACATCAGAAGCCCTTTGAGAGTGGAAGTGAC
AAAATCTCCAAGGAAGTTGTACCGTCTTTGGCCTGTGAATGGTCTCAACTAACCCTTTCAGGTCTAAATGGAGCCCAGATGGAGAAAATACCCCTATTGCATATTTCTTCATGTGACCAAAATATTTCAGAAAAAGACCTATTAGACACAGAGAACAAAAGAAAGAAAGATTTTCTTACTTCAGAGAATTCTTTGCC
ACGTATTTCTAGCCTACCAAAATCAGAGAAGCCATTAAATGAGGAAACAGTGGTAAATAAGAGAGATGAAGAGCAGCATCTTGAATCTCATACAGACTGCATTCTTGCAGTAAAGCAGGCAATATCTGGAACTTCTCCAGTGGCTTCTTCATTTCAGGGTATCAAAAAGTCTATATTCAGAATAAGAGAATCACCTA
AAGAGACTTTCAATGCAAGTTTTTCAGGTCATATGACTGATCCAAACTTTAAAAAAGAAACTGAAGCCTCTGAAAGTGGACTGGAAATACATACTGTTTGCTCACAGAAGGAGGACTCCTTATGTCCAAATTTAATTGATAATGGAAGCTGGCCAGCCACCACCACACAGAATTCTGTAGCTTTGAAGAATGCAGG
TTTAATATCCACTTTGAAAAAGAAAACAAATAAGTTTATTTATGCTATACATGATGAAACATCTTATAAAGGAAAAAAAATACCGAAAGACCAAAAATCAGAACTAATTAACTGTTCAGCCCAGTTTGAAGCAAATGCTTTTGAAGCACCACTTACATTTGCAAATGCTGATTCAGGTTTATTGCATTCTTCTGTGAAAA
GAAGCTGTTCACAGAATGATTCTGAAGAACCAACTTTGTCCTTAACTAGCTCTTTTGGGACAATTCTGAGGAAATGTTCTAGAAATGAAACATGTTCTAATAATACAGTAATCTCTCAGGATCTTGATTATAAAGAAGCAAAATGTAATAAGGAAAAACTACAGTTATTTATTACCCCAGAAGCTGATTCTCTGTCAT
GCCTGCAGGAAGGACAGTGTGAAAATGATCCAAAAAGCAAAAAAGTTTCAGATATAAAAGAAGAGGTCTTGGCTGCAGCATGTCACCCAGTACAACATTCAAAAGTGGAATACAGTGATACTGACTTTCAATCCCAGAAAAGTCTTTTATATGATCATGAAAATGCCAGCACTCTTATTTTAACTCCTACTTCCAAG
GATGTTCTGTCAAACCTAGTCATGATTTCTAGAGGCAAAGAATCATACAAAATGTCAGACAAGCTCAAAGGTAACAATTATGAATCTGATGTTGAATTAACCAAAAATATTCCCATGGAAAAGAATCAAGATGTATGTGCTTTAAATGAAAATTATAAAAACGTTGAGCTGTTGCCACCTGAAAAATACATGAGAGTA
GCATCACCTTCAAGAAAGGTACAATTCAACCAAAACACAAATCTAAGAGTAATCCAAAAAAATCAAGAAGAAACTACTTCAATTTCAAAAATAACTGTCAATCCAGACTCTGAAGAACTTTTCTCAGACAATGAGAATAATTTTGTCTTCCAAGTAGCTAATGAAAGGAATAATCTTGCTTTAGGAAATACTAAGGAAC
TTCATGAAACAGACTTGACTTGTGTAAACGAACCCATTTTCAAGAACTCTACCATGGTTTTATATGGAGACACAGGTGATAAACAAGCAACCCAAGTGTCAATTAAAAAAGATTTGGTTTATGTTCTTGCAGAGGAGAACAAAAATAGTGTAAAGCAGCATATAAAAATGACTCTAGGTCAAGATTTAAAATCGGAC
ATCTCCTTGAATATAGATAAAATACCAGAAAAAAATAATGATTACATGAACAAATGGGCAGGACTCTTAGGTCCAATTTCAAATCACAGTTTTGGAGGTAGCTTCAGAACAGCTTCAAATAAGGAAATCAAGCTCTCTGAACATAACATTAAGAAGAGCAAAATGTTCTTCAAAGATATTGAAGAACAATATCCTACT
AGTTTAGCTTGTGTTGAAATTGTAAATACCTTGGCATTAGATAATCAAAAGAAACTGAGCAAGCCTCAGTCAATTAATACTGTATCTGCACATTTACAGAGTAGTGTAGTTGTTTCTGATTGTAAAAATAGTCATATAACCCCTCAGATGTTATTTTCCAAGCAGGATTTTAATTCAAACCATAATTTAACACCTAGCC
AAAAGGCAGAAATTACAGAACTTTCTACTATATTAGAAGAATCAGGAAGTCAGTTTGAATTTACTCAGTTTAGAAAACCAAGCTACATATTGCAGAAGAGTACATTTGAAGTGCCTGAAAACCAGATGACTATCTTAAAGACCACTTCTGAGGAATGCAGAGATGCTGATCTTCATGTCATAATGAATGCCCCATCG
ATTGGTCAGGTAGACAGCAGCAAGCAATTTGAAGGTACAGTTGAAATTAAACGGAAGTTTGCTGGCCTGTTGAAAAATGACTGTAACAAAAGTGCTTCTGGTTATTTAACAGATGAAAATGAAGTGGGGTTTAGGGGCTTTTATTCTGCTCATGGCACAAAACTGAATGTTTCTACTGAAGCTCTGCAAAAAGCTG
TGAAACTGTTTAGTGATATTGAGAATATTAGTGAGGAAACTTCTGCAGAGGTACATCCAATAAGTTTATCTTCAAGTAAATGTCATGATTCTGTTGTTTCAATGTTTAAGATAGAAAATCATAATGATAAAACTGTAAGTGAAAAAAATAATAAATGCCAACTGATATTACAAAATAATATTGAAATGACTACTGGCACT
TTTGTTGAAGAAATTACTGAAAATTACAAGAGAAATACTGAAAATGAAGATAACAAATATACTGCTGCCAGTAGAAATTCTCATAACTTAGAATTTGATGGCAGTGATTCAAGTAAAAATGATACTGTTTGTATTCATAAAGATGAAACGGACTTGCTATTTACTGATCAGCACAACATATGTCTTAAATTATCTGGCC
AGTTTATGAAGGAGGGAAACACTCAGATTAAAGAAGATTTGTCAGATTTAACTTTTTTGGAAGTTGCGAAAGCTCAAGAAGCATGTCATGGTAATACTTCAAATAAAGAACAGTTAACTGCTACTAAAACGGAGCAAAATATAAAAGATTTTGAGACTTCTGATACATTTTTTCAGACTGCAAGTGGGAAAAATATTA
GTGTCGCCAAAGAGTCATTTAATAAAATTGTAAATTTCTTTGATCAGAAACCAGAAGAATTGCATAACTTTTCCTTAAATTCTGAATTACATTCTGACATAAGAAAGAACAAAATGGACATTCTAAGTTATGAGGAAACAGACATAGTTAAACACAAAATACTGAAAGAAAGTGTCCCAGTTGGTACTGGAAATCAACT
AGTGACCTTCCAGGGACAACCCGAACGTGATGAAAAGATCAAAGAACCTACTCTGTTGGGTTTTCATACAGCTAGCGGGAAAAAAGTTAAAATTGCAAAGGAATCTTTGGACAAAGTGAAAAACCTTTTTGATGAAAAAGAGCAAGGTACTAGTGAAATCACCAGTTTTAGCCATCAATGGGCAAAGACCCTAAA
GTACAGAGAGGCCTGTAAAGACCTTGAATTAGCATGTGAGACCATTGAGATCACAGCTGCCCCAAAGTGTAAAGAAATGCAGAATTCTCTCAATAATGATAAAAACCTTGTTTCTATTGAGACTGTGGTGCCACCTAAGCTCTTAAGTGATAATTTATGTAGACAAACTGAAAATCTCAAAACATCAAAAAGTATCT
TTTTGAAAGTTAAAGTACATGAAAATGTAGAAAAAGAAACAGCAAAAAGTCCTGCAACTTGTTACACAAATCAGTCCCCTTATTCAGTCATTGAAAATTCAGCCTTAGCTTTTTACACAAGTTGTAGTAGAAAAACTTCTGTGAGTCAGACTTCATTACTTGAAGCAAAAAAATGGCTTAGAGAAGGAATATTTGATG
GTCAACCAGAAAGAATAAATACTGCAGATTATGTAGGAAATTATTTGTATGAAAATAATTCAAACAGTACTATAGCTGAAAATGACAAAAATCATCTCTCCGAAAAACAAGATACTTATTTAAGTAACAGTAGCATGTCTAACAGCTATTCCTACCATTCTGATGAGGTATATAATGATTCAGGATATCTCTCAAAAAA
TAAACTTGATTCTGGTATTGAGCCAGTATTGAAGAATGTTGAAGATCAAAAAAACACTAGTTTTTCCAAAGTAATATCCAATGTAAAAGATGCAAATGCATACCCACAAACTGTAAATGAAGATATTTGCGTTGAGGAACTTGTGACTAGCTCTTCACCCTGCAAAAATAAAAATGCAGCCATTAAATTGTCCATATC
TAATAGTAATAATTTTGAGGTAGGGCCACCTGCATTTAGGATAGCCAGTGGTAAAATCGTTTGTGTTTCACATGAAACAATTAAAAAAGTGAAAGACATATTTACAGACAGTTTCAGTAAAGTAATTAAGGAAAACAACGAGAATAAATCAAAAATTTGCCAAACGAAAATTATGGCAGGTTGTTACGAGGCATTGG
ATGATTCAGAGGATATTCTTCATAACTCTCTAGATAATGATGAATGTAGCACGCATTCACATAAGGTTTTTGCTGACATTCAGAGTGAAGAAATTTTACAACATAACCAAAATATGTCTGGATTGGAGAAAGTTTCTAAAATATCACCTTGTGATGTTAGTTTGGAAACTTCAGATATATGTAAATGTAGTATAGGGA
AGCTTCATAAGTCAGTCTCATCTGCAAATACTTGTGGGATTTTTAGCACAGCAAGTGGAAAATCTGTCCAGGTATCAGATGCTTCATTACAAAACGCAAGACAAGTGTTTTCTGAAATAGAAGATAGTACCAAGCAAGTCTTTTCCAAAGTATTGTTTAAAAGTAACGAACATTCAGACCAGCTCACAAGAGAAGAA
AATACTGCTATACGTACTCCAGAACATTTAATATCCCAAAAAGGCTTTTCATATAATGTGGTAAATTCATCTGCTTTCTCTGGATTTAGTACAGCAAGTGGAAAGCAAGTTTCCATTTTAGAAAGTTCCTTACACAAAGTTAAGGGAGTGTTAGAGGAATTTGATTTAATCAGAACTGAGCATAGTCTTCACTATTCA
CCTACGTCTAGACAAAATGTATCAAAAATACTTCCTCGTGTTGATAAGAGAAACCCAGAGCACTGTGTAAACTCAGAAATGGAAAAAACCTGCAGTAAAGAATTTAAATTATCAAATAACTTAAATGTTGAAGGTGGTTCTTCAGAAAATAATCACTCTATTAAAGTTTCTCCATATCTCTCTCAATTTCAACAAGACA
AACAACAGTTGGTATTAGGAACCAAAGTCTCACTTGTTGAGAACATTCATGTTTTGGGAAAAGAACAGGCTTCACCTAAAAACGTAAAAATGGAAATTGGTAAAACTGAAACTTTTTCTGATGTTCCTGTGAAAACAAATATAGAAGTTTGTTCTACTTACTCCAAAGATTCAGAAAACTACTTTGAAACAGAAGCAG
TAGAAATTGCTAAAGCTTTTATGGAAGATGATGAACTGACAGATTCTAAACTGCCAAGTCATGCCACACATTCTCTTTTTACATGTCCCGAAAATGAGGAAATGGTTTTGTCAAATTCAAGAATTGGAAAAAGAAGAGGAGAGCCCCTTATCTTAGTGGGAGAACCCTCAATCAAAAGAAACTTATTAAATGAATTT
GACAGGATAATAGAAAATCAAGAAAAATCCTTAAAGGCTTCAAAAAGCACTCCAGATGGCACAATAAAAGATCGAAGATTGTTTATGCATCATGTTTCTTTAGAGCCGATTACCTGTGTACCCTTTCGCACAACTAAGGAACGTCAAGAGATACAGAATCCAAATTTTACCGCACCTGGTCAAGAATTTCTGTCTAA
ATCTCATTTGTATGAACATCTGACTTTGGAAAAATCTTCAAGCAATTTAGCAGTTTCAGGACATCCATTTTATCAAGTTTCTGCTACAAGAAATGAAAAAATGAGACACTTGATTACTACAGGCAGACCAACCAAAGTCTTTGTTCCACCTTTTAAAACTAAATCACATTTTCACAGAGTTGAACAGTGTGTTAGGAAT
ATTAACTTGGAGGAAAACAGACAAAAGCAAAACATTGATGGACATGGCTCTGATGATAGTAAAAATAAGATTAATGACAATGAGATTCATCAGTTTAACAAAAACAACTCCAATCAAGCAGCAGCTGTAACTTTCACAAAGTGTGAAGAAGAACCTTTAGATTTAATTACAAGTCTTCAGAATGCCAGAGATATACAG
GATATGCGAATTAAGAAGAAACAAAGGCAACGCGTCTTTCCACAGCCAGGCAGTCTGTATCTTGCAAAAACATCCACTCTGCCTCGAATCTCTCTGAAAGCAGCAGTAGGAGGCCAAGTTCCCTCTGCGTGTTCTCATAAACAGCTGTATACGTATGGCGTTTCTAAACATTGCATAAAAATTAACAGCAAAAATG
CAGAGTCTTTTCAGTTTCACACTGAAGATTATTTTGGTAAGGAAAGTTTATGGACTGGAAAAGGAATACAGTTGGCTGATGGTGGATGGCTCATACCCTCCAATGATGGAAAGGCTGGAAAAGAAGAATTTTATAGGGCTCTGTGTGACACTCCAGGTGTGGATCCAAAGCTTATTTCTAGAATTTGGGTTTATAA
TCACTATAGATGGATCATATGGAAACTGGCAGCTATGGAATGTGCCTTTCCTAAGGAATTTGCTAATAGATGCCTAAGCCCAGAAAGGGTGCTTCTTCAACTAAAATACAGATATGATACGGAAATTGATAGAAGCAGAAGATCGGCTATAAAAAAGATAATGGAAAGGGATGACACAGCTGCAAAAACACTTGTT
CTCTGTGTTTCTGACATAATTTCATTGAGCGCAAATATATCTGAAACTTCTAGCAATAAAACTAGTAGTGCAGATACCCAAAAAGTGGCCATTATTGAACTTACAGATGGGTGGTATGCTGTTAAGGCCCAGTTAGATCCTCCCCTCTTAGCTGTCTTAAAGAATGGCAGACTGACAGTTGGTCAGAAGATTATTCT
TCATGGAGCAGAACTGGTGGGCTCTCCTGATGCCTGTACACCTCTTGAAGCCCCAGAATCTCTTATGTTAAAGATTTCTGCTAACAGTACTCGGCCTGCTCGCTGGTATACCAAACTTGGATTCTTTCCTGACCCTAGACCTTTTCCTCTGCCCTTATCATCGCTTTTCAGTGATGGAGGAAATGTTGGTTGTGT
TGATGTAATTATTCAAAGAGCATACCCTATACAGTGGATGGAGAAGACATCATCTGGATTATACATATTTCGCAATGAAAGAGAGGAAGAAAAGGAAGCAGCAAAATATGTGGAGGCCCAACAAAAGAGACTAGAAGCCTTATTCACTAAAATTCAGGAGGAATTTGAAGAACATGAAGAAAACACAACAAAACCA
TATTTACCATCACGTGCACTAACAAGACAGCAAGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTGAAGAATGCAGCAGACCCAGCTTACCTTGAGGGTTATTTCAGTGAAGAGCAGTTAAGAGCCTTGAATAATCACAGGCAAATGTTGAATGATAAGAAACAAGCTCAGATCCAGTTGGAAATT
AGGAAGGCCATGGAATCTGCTGAACAAAAGGAACAAGGTTTATCAAGGGATGTCACAACCGTGTGGAAGTTGCGTATTGTAAGCTATTCAAAAAAAGAAAAAGATTCAGTTATACTGAGTATTTGGCGTCCATCATCAGATTTATATTCTCTGTTAACAGAAGGAAAGAGATACAGAATTTATCATCTTGCAACTTC
AAAATCTAAAAGTAAATCTGAAAGAGCTAACATACAGTTAGCAGCGACAAAAAAAACTCAGTATCAACAACTACCGGTTTCAGATGAAATTTTATTTCAGATTTACCAGCCACGGGAGCCCCTTCACTTCAGCAAATTTTTAGATCCAGACTTTCAGCCATCTTGTTCTGAGGTGGACCTAATAGGATTTGTCGTTT
CTGTTGTGAAAAAAACAGGACTTGCCCCTTTCGTCTATTTGTCAGACGAATGTTACAATTTACTGGCAATAAAGTTTTGGATAGACCTTAATGAGGACATTATTAAGCCTCATATGTTAATTGCTGCAAGCAACCTCCAGTGGCGACCAGAATCCAAATCAGGCCTTCTTACTTTATTTGCTGGAGATTTTTCTGTG
TTTTCTGCTAGTCCAAAAGAGGGCCACTTTCAAGAGACATTCAACAAAATGAAAAATACTGTTGAGAATATTGACATACTTTGCAATGAAGCAGAAAACAAGCTTATGCATATACTGCATGCAAATGATCCCAAGTGGTCCACCCCAACTAAAGACTGTACTTCAGGGCCGTACACTGCTCAAATCATTCCTGGTAC
AGGAAACAAGCTTCTGATGTCTTCTCCTAATTGTGAGATATATTATCAAAGTCCTTTATCACTTTGTATGGCCAAAAGGAAGTCTGTTTCCACACCTGTCTCAGCCCAGATGACTTCAAAGTCTTGTAAAGGGGAGAAAGAGATTGATGACCAAAAGAACTGCAAAAAGAGAAGAGCCTTGGATTTCTTGAGTAGA
CTGCCTTTACCTCCACCTGTTAGTCCCATTTGTACATTTGTTTCTCCGGCTGCACAGAAGGCATTTCAGCCACCAAGGAGTTGTGGCACCAAATACGAAACACCCATAAAGAAAAAAGAACTGAATTCTCCTCAGATGACTCCATTTAAAAAATTCAATGAAATTTCTCTTTTGGAAAGTAATTCAATAGCTGACGA
AGAACTTGCATTGATAAATACCCAAGCTCTTTTGTCTGGTTCAACAGGAGAAAAACAATTTATATCTGTCAGTGAATCCACTAGGACTGCTCCCACCAGTTCAGAAGATTATCTCAGACTGAAACGACGTTGTACTACATCTCTGATCAAAGAACAGGAGAGTTCCCAGGCCAGTACGGAAGAATGTGAGAAAAAT
AAGCAGGACACAATTACAACTAAAAAATATATCTAAGCATTTGCAAAGGCGACAATAAATTATTGACGCTTAACCTTTCCAGTTTATAAGACTGGAATATAATTTCAAACCACACATTAGTACTTATGTTGCACAATGAGAAAAGAAATTAGTTTCAAATTTACCTCAGCGTTTGTGTATCGGGCAAAAATCGTTTTGC
CCGATTCCGTATTGGTATACTTTTGCTTCAGTTGCATATCTTAAAACTAAATGTAATTTATTAACTAATCAAGAAAAACATCTTTGGCTGAGCTCGGTGGCTCATGCCTGTAATCCCAACACTTTGAGAAGCTGAGGTGGGAGGAGTGCTTGAGGCCAGGAGTTCAAGACCAGCCTGGGCAACATAGGGAGACCC
CCATCTTTACGAAGAAAAAAAAAAAGGGGAAAAGAAAATCTTTTAAATCTTTGGATTTGATCACTACAAGTATTATTTTACAATCAACAAAATGGTCATCCAAACTCAAACTTGAGAAAATATCTTGCTTTCAAATTGACACTA
GGCTTTAAGTATCCATGGCTTTAAGTATCCATGGCTTTAAGTATCCATGGCTTTAAGTATCCAT

15. ―Founder Effect‖
• The majority of people tested have a unique mutation –
one that is specific to them and their family.
– Hundreds of unique mutations have been found.
– Some are recurring, however.
• Ashkenazi Jewish population has 3 specific genes that
recur: Two BRCA1 and One BRCA2
– 185delAG; 5382insC; 6174delT
– 1996 study by Muto,et.al:
• 19% of Jewish women with ovarian cancer in Mass and
Israel had 185delAG
• 12% of breast cancers in Ashkenazi Jews are attributable to
BRCA 1 or BRCA 2 (Journal of National Cancer Institute,
1999)
– Genes come from groups of people who do not go
out of their small groups to find a mate
(interbreeding).

16. How do you get the bad gene?

17. BRCA Mutation Increases Breast
and Ovarian Cancer Risks
AJHG 1995;56:265-271
Science 2003: 643-646
JCO 2005 23 (8): 1656-63
NCI 2005
20
40
60
80
100
Breast cancer
by age 50
Breast cancer
by age 70
Ovarian cancer
by age 70
2%
Up to
50%
8%
Up to
87%
RiskofCancer(%)
<1%
Up to
44%
General Population
BRCA Mutation
Lancet 1994;343:692-695
NEJM 1997;336:1401-1408
AJHG 2003;72:1117-1130

18. BRCA Mutation Increases Risk
of Second Breast Cancer
Lancet 1998;351:316-21
JCO 2004;22:2328-35
Lancet 1994;3343:692-5
Gynecol Oncol. 2005 Jan;96(1):222-6
0
20
40
60
Breast Cancer
after 5 years
Breast Cancer
by age 70
Up to
3.5%
Up to
27%
Up to
11%
Up to
64%
RiskofCancer(%)
General Population
BRCA Mutation
Ca Epi Biomarkers Prev. 1999;8(10):855-61
JNCI 1999;15:1310-6
JCO 1998;16:2417-25

19. Risks in Men With a
BRCA Mutation
JCO 2004;22:
735-42
Breast Cancer
by age 80
Prostate Cancer
by age 80
General Population
BRCA Mutation*
5
10
15
20
25
<1%
7%
15%
20%
RiskofCancer(%)
*Risks refer to BRCA2 mutation carriers.
Risks for male BRCA1 mutation carriers are less characterized

20. ―Red Flags‖ for Hereditary Breast
and Ovarian Cancer Syndrome
• For Women or Men with a newly diagnosed breast
cancer:
– Diagnosed at < 45 with or without FH
– Diagnosed at 45-50 with at a least one close blood relative
with breast cancer and/or at least one close blood relative
with ovarian cancer. Some would test all women in their
40s
– Bilateral breast cancer
– Diagnosed >50 with two or more close blood relatives with
breast or ovarian cancer at any age
– Close male relative with breast cancer
– Personal history of ovarian cancer
– Specific ethnicity associated with founder mutations
(Ashkenazi Jewish, Icelandic, Swedish, Hungarian)
especially along with family history

21. ―Red Flags‖ for Women & Men
who do not have Cancer
• Women or Men who do not currently have cancer are at
risk:
– Family member with known BRCA 1 or BRCA 2 mutation
– Previous history of breast cancer from the previously stated risk
factors. (The test has only been available for ten years)
– Personal history of ovarian cancer
– One or more close male relatives with breast cancer
– Two or more female relatives with breast cancer especially at age <50
on either maternal or paternal side
– One or more close female relatives with ovarian cancer
– Specific ethnicity as stated previously along with family history
• REMEMBER: The family member who had the cancer
diagnosis should always be tested FIRST if possible.

22. Family History Considerations
• One-half of BRCA carriers inherit the
mutation from their father
• Ovarian cancer is a very important
indicator
• Early onset breast cancer is more
important than the number of affected
family members
Science
2003:302(5645):643-6

23. New Considerations
• Triple Negative Breast Cancer:
– Research has shown that women who have breast
cancer not sensitive to hormones or a drug called
Herceptin are more inclined to have the BRCA
gene even without a family history.
– Testing is indicated if you have triple negative
breast cancer under age 60
• Pancreatic Cancer:
– If two or more people in the family have had
pancreatic cancer that may be a criteria for testing
– The gene will be found in 17-19% of those families

24. Prevalence of BRCA
Mutations – Non Jewish
www.brcacalculator.com
Ovarian cancer
in one relative,
no breast
cancer <50
21.1%23.1%8.8%
Ovarian
cancer, no
breast cancer
16.9%15.8%6.8%
Breast
cancer <50
5.6%4.5%2.8%
No breast
or ovarian
cancer
Breast cancer
<50, no ovarian
cancer
No breast cancer
<50 or ovarian
cancer
Patient‟s
History
Family History

25. Prevalence of Mutations in
Ashkenazi Jewish Individuals
www.brcacalculator.com
42.0%37.0%22.2%
Ovarian
cancer, no
breast cancer
38.8%24.2%12.0%
Breast
cancer <50
15.6%13.7%6.9%
No breast
or ovarian
cancer
Breast cancer
<50, no ovarian
cancer
No breast cancer
<50 or ovarian
cancer
Patient‟s
History
Family History
Ovarian cancer
in one relative,
no breast
cancer <50

26. Genetic Testing
• Benefits
– Allows for individualized medical
management
– Accurate risk assessment
– Alleviates uncertainty and anxiety
• Limitations
– Genetic testing for BRCA1 and BRCA2
does not identify all causes of
hereditary breast or ovarian cancer
© 2007 Myriad Genetic
Laboratories, Inc.

27. Interpreting Test Results
• Positive for a deleterious mutation
• No mutation detected (negative test)
– Mutation has been previously
identified in the family
– No known mutation in the family or
the family hasn‘t been tested
• Genetic variant of uncertain significance
© 2007 Myriad Genetic
Laboratories, Inc.

28. Positive for a
Deleterious Mutation
• BRCA-associated cancer risks
• 50% chance for first degree relatives to
have the same mutation
– Children
– Siblings
– Parents
• Test relatives for identified familial
mutation
© 2007 Myriad Genetic
Laboratories, Inc.

29. Negative Test (no
mutation detected)
• Does not mean that the patient cannot
or will not develop breast cancer.
• Only means that they are not at risk
for developing hereditary breast
cancer related to the BRCA mutations
for which they were tested.

30. Negative Test (no
mutation detected)
• Family History is positive for the gene
• General population cancer risks—if no
cancer history on the other side of the
family
• Avoid unnecessary screening/surgery
• Can‘t pass on the gene
• Family History is negative or unknown for
the gene
• Most difficult to interpret
• Risk is based on total family history and
can still be significant.
© 2007 Myriad Genetic
Laboratories, Inc.

31. Family History & BRCA
Positive and Negative
CancerRisks%
50
Age (Years)
30 50 70
Positive for deleterious
BRCA mutation
100
Risk based on family
history
Negative for familial
BRCA mutation
Reprinted with permission from Ponder B: Genetic Testing for Cancer Risk. Science 1997; 278:1050-4.
Copyright 1997 American Association for the Advancement of Science

32. Genetic Variant of
uncertain significance
• Clinical significance not yet known. It
is neither positive or negative.
• Manage based on personal and family
cancer history.
• May be further clarified, and then re-
classified as positive or negative later
on as more information is identified.
© 2007 Myriad Genetic
Laboratories, Inc.

33. Managing Hereditary
Cancer Risk
• Surveillance
• Chemoprevention
• Prophylactic surgery
*Individual risk reduction may vary
based on personal health history

34. Screening for
Ovarian Cancer
• Screening for Familial Ovarian Cancer
– Poor Survival
– Most cancers are diagnosed at Stage 3 and 4
– Transvaginal U.S. & CA 125 are ineffective in
detecting tumors at a sufficiently early stage to
influence survival. Only detect 57% stage 1
– Ovarian cancer is 1/8 as common as breast, but
3 times more lethal
• Should be followed by an OB/GYN

35. Prophylactic Oophorectomy
• Recommend bilateral salpingo-
oophorectomy (BSO) at age 35 or after
childbearing is complete
– ~96% ovarian cancer risk reduction in
BRCA carriers
– Can reduce breast cancer risk by up to
68% for both BRCA1 and BRCA2
mutation carriers if the woman is pre-
menopausal
JAMA. 2006;296:185-92
Clin Oncol. 2005 Mar
10;23(8):1656-63

36. Prophylactic Ovarian removal -
Bilateral Oophorectomy (BSO)
• Does HRT increase cancer risk after
oophorectomy (ovarian removal)?
– No measurable effect with ―short term
usage‖ of Estrogen alone
– Estrogen until menopausal age – 50
• Unopposed estrogen does increase the
risk of uterine cancer. Adding a
hysterectomy to the BSO would
eliminate that risk, however, a much
bigger operation.

37. Surveillance for Breast Cancer
www.nccn.org
Cancer
Procedure Age to begin Frequency
Breast self-exam 18 yrs Monthly
Clinical breast
exam
25 yrs Twice a year
Mammography 25 yrs Yearly
MRI 25 yrs Yearly

38. Screening with MRI in
BRCA patients
• JAMA, 2004: MRI most
sensitive in detecting cancer
and can decrease mortality
in high risk women.
• Adequacy of screening
women with BRCA mutations
with only Mammo was not
shown to be good enough
even if the women had fatty
or low-dense breasts.
• Waiting a year between
screening is too long –
BRCA patient‘s cancers grow
faster than sporadic cancers.

39. Chemoprevention of
Breast Cancer
Tamoxifen
• Selective Estrogen Receptor Modulator (SERM)
– it blocks hormones from affecting breast cells
• Affected BRCA carriers: 50% decrease for
contralateral breast cancer
• Unaffected BRCA2 carriers: 62% decrease in
the risk of cancer
• Unaffected high-risk: 45% decrease
• Risks – increased risk of uterine cancer and
clotting. Low risk in women who took the
medication under age 50
Int J Cancer.
2006;118(9):2281-4
Lancet 2000;356:1876-81

40. Prophylactic Mastectomy
• Greater than 90% breast
cancer risk reduction
in BRCA carriers. May be
has high as 95-98%
reduction
• 100 women having
prophylactic surgery 1995-
2006
• 18/100 had abnormal lesions
• 3 invasive cancer
• 8 in situ cancer
• 7 ADH
•Eur J Surg Oncol 2008,
April 21

41. Reconstruction after Mastectomy
has come a long way
Postoperative left mastectomy – left latissimus flap and implant
Pre-operative view

42. Nipple Sparing Mastectomy

43. Insurance Coverage of
Genetic Testing
• All major carriers provide coverage for
genetic testing
• Established guidelines
– Medicare
– Most major carriers
– Some insurance companies have genetic
exclusions and will not pay no matter what the
indication - rare
• Cost: $3,350
• Cost if known family mutation: $450
• Supreme Court ruling may allow other
companies to compete and the price may go
down © 2007 Myriad Genetic

44. Genetic Discrimination
• Federal and state laws prohibit the use of
genetic information as a ‗pre-existing
condition‘
– Federal HIPAA legislation
– The majority of states have additional
laws
• Over 175,000 clinical tests performed to date
• No documented cases of genetic
discrimination
AJHG
2000;66:293

45. Gina Legislation
• U.S. President George
W. Bush signed into law
May 21, 2008 the first
civil rights legislation of
the new millennium, the
Genetic Information
Nondiscrimination Act
(GINA).
• GINA is the first and only
federal legislation that will
provide protections
against discrimination
based on an individual‘s
genetic information in
health insurance
coverage and
employment settings.

46. How do you test?
• Talk to your Primary Care Physician
– Your Doctor may feel comfortable with the discussion
and go ahead and test you; or they may send you to a
breast specialist to discuss your risks and whether the
test is right for you.
– The test is either blood or saliva
– The results are available in 2-3 weeks if insurance
approves
• Genetic Counselors
– If your BRCA test is negative but you have a very strong
FH – may need additional testing
• Other rare mutations exist – p53. pTEN/MMAC1
• Dr Jennifer Klemp in Kansas City: 913-588-7750

47. Summary/Case Presentations
1. BRCA 1 and 2 gene increase the risk of breast
and ovarian cancer significantly
2. ―Red Flags‖ such as multiple women with breast
or ovarian cancer in a family, especially at a
young age clue us in to the possibility that the
gene may be present
3. A blood and saliva test is available to identify the
gene
4. Options are available to improve screening and
decrease risk in women who have the gene
© 2007 Myriad Genetic

48. Rachel, age 40 – no cancer

49. Rachel‘s Test result

50. Rachel--Ovarian
Recommendations
• Her risk of ovarian cancer is 40-50%
• She is 40 and has completed child-
bearing
– Recommend: bilateral oophorectomy
(ovary removal) +/- hysterectomy
– Ovarian removal decreases her risk of
breast cancer by over 50%
– Unopposed Estrogen for 10 years okay,
but it increases her risk of uterine cancer if
she doesn‘t have a hysterectomy

51. Rachel – Breast
Recommendations
• Risk of Breast Cancer: 50-87%
• Options
– Increase screening with Mammogram and
MRI yearly separated by 6 months
– Above + Tamoxifen for 5 years to
decrease her risk by 50%
– Bilateral prophylactic mastectomies with
or without reconstruction

52. Rachel – Family
Recommendations
• Consider testing her
Brother – If he tests
Negative then his
daughter couldn‘t
inherit the gene from
him
• Rachel‘s Children –
each has a 50:50
chance of inheriting
the gene.

53. Heather, age 38

54. Heather
• Heather is at risk because her p Aunt
had breast cancer at a young age
• The best person to test would be
– Heather‘s Aunt – the person affected by
cancer
• If her aunt is positive then I would test
– Heather‘s Father
• If he is positive then I would test
– Heather

55. Heather
• Heather‘s aunt was positive
• Heather‘s Dad was negative
• What is Heather‘s risk?
– 10-13%, same as the general population
• Does she or her brother or sister need to
be tested?
– No, their Dad was negative
• Does her uncle and other two aunts need
to be tested?
– Yes, they all have a 50:50 chance of having the
gene.

56. Conclusion
• The BRCA gene is rare, but can
significantly increase the risk of breast and
ovarian cancer in patient‘s who have this
mutation.
• In patients who meet criteria, the test can
easily be done.
• If positive, there are many options
available to follow and potentially prevent
cancer.

57. Questions?