Breast cancer genetic testing: Is it right for you?

Patty Tenofsky, MD FACSWomen’s Connection

October 8, 2013

Angelina Jolie

Marcheline Bertrand

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.

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

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%

Most Women Develop Breast Cancer WITHOUT a Family History

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

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)

Sickle Cell Anemia – only one base code incorrect

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.

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.

Human Chromosomes

Laboratory Testing for Genetic Mutations

• BRCA1: > 5,500 bp– AGCTCGCTGAGACTTCCTGGACCCCGCACCAGGCTGTGGGGTTTCTCAGATAACTGGGCCCCTGCGCTCAGGAGGCCTTCACCCTCTGCTCTGGGTAAAGTTCATTGGAACAGAAAGAAATGGATTTATCTGCTCTTCGCGTTGAAGAAGTACAAAATGTCATTAATGCTATGCAGAAAATCTTAGAGTGTCCCATCTGTCTGGAGTT

GATCAAGGAACCTGTCTCCACAAAGTGTGACCACATATTTTGCAAATTTTGCATGCTGAAACTTCTCAACCAGAAGAAAGGGCCTTCACAGTGTCCTTTATGTAAGAATGATATAACCAAAAGGAGCCTACAAGAAAGTACGAGATTTAGTCAACTTGTTGAAGAGCTATTGAAAATCATTTGTGCTTTTCAGCTTGACACAGGTTTGGAGTATGCAAACAGCTATAATTTTGCAAAAAAGGAAAATAACTCTCCTGAACATCTAAAAGATGAAGTTTCTATCATCCAAAGTATGGGCTACAGAAACCGTGCCAAAAGACTTCTACAGAGTGAACCCGAAAATCCTTCCTTGCAGGAAACCAGTCTCAGTGTCCAACTCTCTAACCTTGGAACTGTGAGAACTCTGAGGACAAAGCAGCGGATACAACCTCAAAAGACGTCTGTCTACATTGAATTGGGATCTGATTCTTCTGAAGATACCGTTAATAAGGCAACTTATTGCAGTGTGGGAGATCAAGAATTGTTACAAATCACCCCTCAAGGAACCAGGGATGAAATCAGTTTGGATTCTGCAAAAAAGGCTGCTTGTGAATTTTCTGAGACGGATGTAACAAATACTGAACATCATCAACCCAGTAATAATGATTTGAACACCACTGAGAAGCGTGCAGCTGAGAGGCATCCAGAAAAGTATCAGGGTAGTTCTGTTTCAAACTTGCATGTGGAGCCATGTGGCACAAATACTCATGCCAGCTCATTACAGCATGAGAACAGCAGTTTATTACTCACTAAAGACAGAATGAATGTAGAAAAGGCTGAATTCTGTAATAAAAGCAAACAGCCTGGCTTAGCAAGGAGCCAACATAACAGATGGGCTGGAAGTAAGGAAACATGTAATGATAGGCGGACTCCCAGCACAGAAAAAAAGGTAGATCTGAATGCTGATCCCCTGTGTGAGAGAAAAGAATGGAATAAGCAGAAACTGCCATGCTCAGAGAATCCTAGAGATACTGAAGATGTTCCTTGGATAACACTAAATAGCAGCATTCAGAAAGTTAATGAGTGGTTTTCCAGAAGTGATGAACTGTTAGGTTCTGATGACTCACATGATGGGGAGTCTGAATCAAATGCCAAAGTAGCTGATGTATTGGACGTTCTAAATGAGGTAGATGAATATTCTGGTTCTTCAGAGAAAATAGACTTACTGGCCAGTGATCCTCATGAGGCTTTAATATGTAAAAGTGAAAGAGTTCACTCCAAATCAGTAGAGAGTAATATTGAAGACAAAATATTTGGGAAAACCTATCGGAAGAAGGCAAGCCTCCCCAACTTAAGCCATGTAACTGAAAATCTAATTATAGGAGCATTTGTTACTGAGCCACAGATAATACAAGAGCGTCCCCTCACAAATAAATTAAAGCGTAAAAGGAGACCTACATCAGGCCTTCATCCTGAGGATTTTATCAAGAAAGCAGATTTGGCAGTTCAAAAGACTCCTGAAATGATAAATCAGGGAACTAACCAAACGGAGCAGAATGGTCAAGTGATGAATATTACTAATAGTGGTCATGAGAATAAAACAAAAGGTGATTCTATTCAGAATGAGAAAAATCCTAACCCAATAGAATCACTCGAAAAAGAATCTGCTTTCAAAACGAAAGCTGAACCTATAAGCAGCAGTATAAGCAATATGGAACTCGAATTAAATATCCACAATTCAAAAGCACCTAAAAAGAATAGGCTGAGGAGGAAGTCTTCTACCAGGCATATTCATGCGCTTGAACTAGTAGTCAGTAGAAATCTAAGCCCACCTAATTGTACTGAATTGCAAATTGATAGTTGTTCTAGCAGTGAAGAGATAAAGAAAAAAAAGTACAACCAAATGCCAGTCAGGCACAGCAGAAACCTACAACTCATGGAAGGTAAAGAACCTGCAACTGGAGCCAAGAAGAGTAACAAGCCAAATGAACAGACAAGTAAAAGACATGACAGCGATACTTTCCCAGAGCTGAAGTTAACAAATGCACCTGGTTCTTTTACTAAGTGTTCAAATACCAGTGAACTTAAAGAATTTGTCAATCCTAGCCTTCCAAGAGAAGAAAAAGAAGAGAAACTAGAAACAGTTAAAGTGTCTAATAATGCTGAAGACCCCAAAGATCTCATGTTAAGTGGAGAAAGGGTTTTGCAAACTGAAAGATCTGTAGAGAGTAGCAGTATTTCATTGGTACCTGGTACTGATTATGGCACTCAGGAAAGTATCTCGTTACTGGAAGTTAGCACTCTAGGGAAGGCAAAAACAGAACCAAATAAATGTGTGAGTCAGTGTGCAGCATTTGAAAACCCCAAGGGACTAATTCATGGTTGTTCCAAAGATAATAGAAATGACACAGAAGGCTTTAAGTATCCATTGGGACATGAAGTTAACCACAGTCGGGAAACAAGCATAGAAATGGAAGAAAGTGAACTTGATGCTCAGTATTTGCAGAATACATTCAAGGTTTCAAAGCGCCAGTCATTTGCTCCGTTTTCAAATCCAGGAAATGCAGAAGAGGAATGTGCAACATTCTCTGCCCACTCTGGGTCCTTAAAGAAACAAAGTCCAAAAGTCACTTTTGAATGTGAACAAAAGGAAGAAAATCAAGGAAAGAATGAGTCTAATATCAAGCCTGTACAGACAGTTAATATCACTGCAGGCTTTCCTGTGGTTGGTCAGAAAGATAAGCCAGTTGATAATGCCAAATGTAGTATCAAAGGAGGCTCTAGGTTTTGTCTATCATCTCAGTTCAGAGGCAACGAAACTGGACTCATTACTCCAAATAAACATGGACTTTTACAAAACCCATATCGTATACCACCACTTTTTCCCATCAAGTCATTTGTTAAAACTAAATGTAAGAAAAATCTGCTAGAGGAAAACTTTGAGGAACATTCAATGTCACCTGAAAGAGAAATGGGAAATGAGAACATTCCAAGTACAGTGAGCACAATTAGCCGTAATAACATTAGAGAAAATGTTTTTAAAGAAGCCAGCTCAAGCAATATTAATGAAGTAGGTTCCAGTACTAATGAAGTGGGCTCCAGTATTAATGAAATAGGTTCCAGTGATGAAAACATTCAAGCAGAACTAGGTAGAAACAGAGGGCCAAAATTGAATGCTATGCTTAGATTAGGGGTTTTGCAACCTGAGGTCTATAAACAAAGTCTTCCTGGAAGTAATTGTAAGCATCCTGAAATAAAAAAGCAAGAATATGAAGAAGTAGTTCAGACTGTTAATACAGATTTCTCTCCATATCTGATTTCAGATAACTTAGAACAGCCTATGGGAAGTAGTCATGCATCTCAGGTTTGTTCTGAGACACCTGATGACCTGTTAGATGATGGTGAAATAAAGGAAGATACTAGTTTTGCTGAAAATGACATTAAGGAAAGTTCTGCTGTTTTTAGCAAAAGCGTCCAGAAAGGAGAGCTTAGCAGGAGTCCTAGCCCTTTCACCCATACACATTTGGCTCAGGGTTACCGAAGAGGGGCCAAGAAATTAGAGTCCTCAGAAGAGAACTTATCTAGTGAGGATGAAGAGCTTCCCTGCTTCCAACACTTGTTATTTGGTAAAGTAAACAATATACCTTCTCAGTCTACTAGGCATAGCACCGTTGCTACCGAGTGTCTGTCTAAGAACACAGAGGAGAATTTATTATCATTGAAGAATAGCTTAAATGACTGCAGTAACCAGGTAATATTGGCAAAGGCATCTCAGGAACATCACCTTAGTGAGGAAACAAAATGTTCTGCTAGCTTGTTTTCTTCACAGTGCAGTGAATTGGAAGACTTGACTGCAAATACAAACACCCAGGATCCTTTCTTGATTGGTTCTTCCAAACAAATGAGGCATCAGTCTGAAAGCCAGGGAGTTGGTCTGAGTGACAAGGAATTGGTTTCAGATGATGAAGAAAGAGGAACGGGCTTGGAAGAAAATAATCAAGAAGAGCAAAGCATGGATTCAAACTTAGGTGAAGCAGCATCTGGGTGTGAGAGTGAAACAAGCGTCTCTGAAGACTGCTCAGGGCTATCCTCTCAGAGTGACATTTTAACCACTCAGCAGAGGGATACCATGCAACATAACCTGATAAAGCTCCAGCAGGAAATGGCTGAACTAGAAGCTGTGTTAGAACAGCATGGGAGCCAGCCTTCTAACAGCTACCCTTCCATCATAAGTGACTCTTCTGCCCTTGAGGACCTGCGAAATCCAGAACAAAGCACATCAGAAAAAGCAGTATTAACTTCACAGAAAAGTAGTGAATACCCTATAAGCCAGAATCCAGAAGGCCTTTCTGCTGACAAGTTTGAGGTGTCTGCAGATAGTTCTACCAGTAAAAATAAAGAACCAGGAGTGGAAAGGTCATCCCCTTCTAAATGCCCATCATTAGATGATAGGTGGTACATGCACAGTTGCTCTGGGAGTCTTCAGAATAGAAACTACCCATCTCAAGAGGAGCTCATTAAGGTTGTTGATGTGGAGGAGCAACAGCTGGAAGAGTCTGGGCCACACGATTTGACGGAAACATCTTACTTGCCAAGGCAAGATCTAGAGGGAACCCCTTACCTGGAATCTGGAATCAGCCTCTTCTCTGATGACCCTGAATCTGATCCTTCTGAAGACAGAGCCCCAGAGTCAGCTCGTGTTGGCAACATACCATCTTCAACCTCTGCATTGAAAGTTCCCCAATTGAAAGTTGCAGAATCTGCCCAGAGTCCAGCTGCTGCTCATACTACTGATACTGCTGGGTATAATGCAATGGAAGAAAGTGTGAGCAGGGAGAAGCCAGAATTGACAGCTTCAACAGAAAGGGTCAACAAAAGAATGTCCATGGTGGTGTCTGGCCTGACCCCAGAAGAATTTATGCTCGTGTACAAGTTTGCCAGAAAACACCACATCACTTTAACTAATCTAATTACTGAAGAGACTACTCATGTTGTTATGAAAACAGATGCTGAGTTTGTGTGTGAACGGACACTGAAATATTTTCTAGGAATTGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGGGTGACCCAGTCTATTAAAGAAAGAAAAATGCTGAATGAGCATGATTTTGAAGTCAGAGGAGATGTGGTCAATGGAAGAAACCACCAAGGTCCAAAGCGAGCAAGAGAATCCCAGGACAGAAAGATCTTCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACATGCCCACAGATCAACTGGAATGGATGGTACAGCTGTGTGGTGCTTCTGTGGTGAAGGAGCTTTCATCATTCACCCTTGGCACAGGTGTCCACCCAATTGTGGTTGTGCAGCCAGATGCCTGGACAGAGGACAATGGCTTCCATGCAATTGGGCAGATGTGTGAGGCACCTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGTAGCACTCTACCAGTGCCAGGAGCTGGACACCTACCTGATACCCCAGATCCCCCACAGCCACTACTGACTGCAG

• BRCA2: > 11,000 bp– GGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTGTGGCACTGCTGCGCCTCTGCTGCGCCTCGGGTGTCTTTTGCGGCGGTGGGTCGCCGCCGGGAGAAGCGTGAGGGGACAGATTTGTGACCGGCGCGGTTTTTGTCAGCTTACTCCGGCCAAAAAAGAACTGCACCTCTGGAGCGGACTTATTTACCAAGCA

TTGGAGGAATATCGTAGGTAAAAATGCCTATTGGATCCAAAGAGAGGCCAACATTTTTTGAAATTTTTAAGACACGCTGCAACAAAGCAGATTTAGGACCAATAAGTCTTAATTGGTTTGAAGAACTTTCTTCAGAAGCTCCACCCTATAATTCTGAACCTGCAGAAGAATCTGAACATAAAAACAACAATTACGAACCAAACCTATTTAAAACTCCACAAAGGAAACCATCTTATAATCAGCTGGCTTCAACTCCAATAATATTCAAAGAGCAAGGGCTGACTCTGCCGCTGTACCAATCTCCTGTAAAAGAATTAGATAAATTCAAATTAGACTTAGGAAGGAATGTTCCCAATAGTAGACATAAAAGTCTTCGCACAGTGAAAACTAAAATGGATCAAGCAGATGATGTTTCCTGTCCACTTCTAAATTCTTGTCTTAGTGAAAGTCCTGTTGTTCTACAATGTACACATGTAACACCACAAAGAGATAAGTCAGTGGTATGTGGGAGTTTGTTTCATACACCAAAGTTTGTGAAGGGTCGTCAGACACCAAAACATATTTCTGAAAGTCTAGGAGCTGAGGTGGATCCTGATATGTCTTGGTCAAGTTCTTTAGCTACACCACCCACCCTTAGTTCTACTGTGCTCATAGTCAGAAATGAAGAAGCATCTGAAACTGTATTTCCTCATGATACTACTGCTAATGTGAAAAGCTATTTTTCCAATCATGATGAAAGTCTGAAGAAAAATGATAGATTTATCGCTTCTGTGACAGACAGTGAAAACACAAATCAAAGAGAAGCTGCAAGTCATGGATTTGGAAAAACATCAGGGAATTCATTTAAAGTAAATAGCTGCAAAGACCACATTGGAAAGTCAATGCCAAATGTCCTAGAAGATGAAGTATATGAAACAGTTGTAGATACCTCTGAAGAAGATAGTTTTTCATTATGTTTTTCTAAATGTAGAACAAAAAATCTACAAAAAGTAAGAACTAGCAAGACTAGGAAAAAAATTTTCCATGAAGCAAACGCTGATGAATGTGAAAAATCTAAAAACCAAGTGAAAGAAAAATACTCATTTGTATCTGAAGTGGAACCAAATGATACTGATCCATTAGATTCAAATGTAGCACATCAGAAGCCCTTTGAGAGTGGAAGTGACAAAATCTCCAAGGAAGTTGTACCGTCTTTGGCCTGTGAATGGTCTCAACTAACCCTTTCAGGTCTAAATGGAGCCCAGATGGAGAAAATACCCCTATTGCATATTTCTTCATGTGACCAAAATATTTCAGAAAAAGACCTATTAGACACAGAGAACAAAAGAAAGAAAGATTTTCTTACTTCAGAGAATTCTTTGCCACGTATTTCTAGCCTACCAAAATCAGAGAAGCCATTAAATGAGGAAACAGTGGTAAATAAGAGAGATGAAGAGCAGCATCTTGAATCTCATACAGACTGCATTCTTGCAGTAAAGCAGGCAATATCTGGAACTTCTCCAGTGGCTTCTTCATTTCAGGGTATCAAAAAGTCTATATTCAGAATAAGAGAATCACCTAAAGAGACTTTCAATGCAAGTTTTTCAGGTCATATGACTGATCCAAACTTTAAAAAAGAAACTGAAGCCTCTGAAAGTGGACTGGAAATACATACTGTTTGCTCACAGAAGGAGGACTCCTTATGTCCAAATTTAATTGATAATGGAAGCTGGCCAGCCACCACCACACAGAATTCTGTAGCTTTGAAGAATGCAGGTTTAATATCCACTTTGAAAAAGAAAACAAATAAGTTTATTTATGCTATACATGATGAAACATCTTATAAAGGAAAAAAAATACCGAAAGACCAAAAATCAGAACTAATTAACTGTTCAGCCCAGTTTGAAGCAAATGCTTTTGAAGCACCACTTACATTTGCAAATGCTGATTCAGGTTTATTGCATTCTTCTGTGAAAAGAAGCTGTTCACAGAATGATTCTGAAGAACCAACTTTGTCCTTAACTAGCTCTTTTGGGACAATTCTGAGGAAATGTTCTAGAAATGAAACATGTTCTAATAATACAGTAATCTCTCAGGATCTTGATTATAAAGAAGCAAAATGTAATAAGGAAAAACTACAGTTATTTATTACCCCAGAAGCTGATTCTCTGTCATGCCTGCAGGAAGGACAGTGTGAAAATGATCCAAAAAGCAAAAAAGTTTCAGATATAAAAGAAGAGGTCTTGGCTGCAGCATGTCACCCAGTACAACATTCAAAAGTGGAATACAGTGATACTGACTTTCAATCCCAGAAAAGTCTTTTATATGATCATGAAAATGCCAGCACTCTTATTTTAACTCCTACTTCCAAGGATGTTCTGTCAAACCTAGTCATGATTTCTAGAGGCAAAGAATCATACAAAATGTCAGACAAGCTCAAAGGTAACAATTATGAATCTGATGTTGAATTAACCAAAAATATTCCCATGGAAAAGAATCAAGATGTATGTGCTTTAAATGAAAATTATAAAAACGTTGAGCTGTTGCCACCTGAAAAATACATGAGAGTAGCATCACCTTCAAGAAAGGTACAATTCAACCAAAACACAAATCTAAGAGTAATCCAAAAAAATCAAGAAGAAACTACTTCAATTTCAAAAATAACTGTCAATCCAGACTCTGAAGAACTTTTCTCAGACAATGAGAATAATTTTGTCTTCCAAGTAGCTAATGAAAGGAATAATCTTGCTTTAGGAAATACTAAGGAACTTCATGAAACAGACTTGACTTGTGTAAACGAACCCATTTTCAAGAACTCTACCATGGTTTTATATGGAGACACAGGTGATAAACAAGCAACCCAAGTGTCAATTAAAAAAGATTTGGTTTATGTTCTTGCAGAGGAGAACAAAAATAGTGTAAAGCAGCATATAAAAATGACTCTAGGTCAAGATTTAAAATCGGACATCTCCTTGAATATAGATAAAATACCAGAAAAAAATAATGATTACATGAACAAATGGGCAGGACTCTTAGGTCCAATTTCAAATCACAGTTTTGGAGGTAGCTTCAGAACAGCTTCAAATAAGGAAATCAAGCTCTCTGAACATAACATTAAGAAGAGCAAAATGTTCTTCAAAGATATTGAAGAACAATATCCTACTAGTTTAGCTTGTGTTGAAATTGTAAATACCTTGGCATTAGATAATCAAAAGAAACTGAGCAAGCCTCAGTCAATTAATACTGTATCTGCACATTTACAGAGTAGTGTAGTTGTTTCTGATTGTAAAAATAGTCATATAACCCCTCAGATGTTATTTTCCAAGCAGGATTTTAATTCAAACCATAATTTAACACCTAGCCAAAAGGCAGAAATTACAGAACTTTCTACTATATTAGAAGAATCAGGAAGTCAGTTTGAATTTACTCAGTTTAGAAAACCAAGCTACATATTGCAGAAGAGTACATTTGAAGTGCCTGAAAACCAGATGACTATCTTAAAGACCACTTCTGAGGAATGCAGAGATGCTGATCTTCATGTCATAATGAATGCCCCATCGATTGGTCAGGTAGACAGCAGCAAGCAATTTGAAGGTACAGTTGAAATTAAACGGAAGTTTGCTGGCCTGTTGAAAAATGACTGTAACAAAAGTGCTTCTGGTTATTTAACAGATGAAAATGAAGTGGGGTTTAGGGGCTTTTATTCTGCTCATGGCACAAAACTGAATGTTTCTACTGAAGCTCTGCAAAAAGCTGTGAAACTGTTTAGTGATATTGAGAATATTAGTGAGGAAACTTCTGCAGAGGTACATCCAATAAGTTTATCTTCAAGTAAATGTCATGATTCTGTTGTTTCAATGTTTAAGATAGAAAATCATAATGATAAAACTGTAAGTGAAAAAAATAATAAATGCCAACTGATATTACAAAATAATATTGAAATGACTACTGGCACTTTTGTTGAAGAAATTACTGAAAATTACAAGAGAAATACTGAAAATGAAGATAACAAATATACTGCTGCCAGTAGAAATTCTCATAACTTAGAATTTGATGGCAGTGATTCAAGTAAAAATGATACTGTTTGTATTCATAAAGATGAAACGGACTTGCTATTTACTGATCAGCACAACATATGTCTTAAATTATCTGGCCAGTTTATGAAGGAGGGAAACACTCAGATTAAAGAAGATTTGTCAGATTTAACTTTTTTGGAAGTTGCGAAAGCTCAAGAAGCATGTCATGGTAATACTTCAAATAAAGAACAGTTAACTGCTACTAAAACGGAGCAAAATATAAAAGATTTTGAGACTTCTGATACATTTTTTCAGACTGCAAGTGGGAAAAATATTAGTGTCGCCAAAGAGTCATTTAATAAAATTGTAAATTTCTTTGATCAGAAACCAGAAGAATTGCATAACTTTTCCTTAAATTCTGAATTACATTCTGACATAAGAAAGAACAAAATGGACATTCTAAGTTATGAGGAAACAGACATAGTTAAACACAAAATACTGAAAGAAAGTGTCCCAGTTGGTACTGGAAATCAACTAGTGACCTTCCAGGGACAACCCGAACGTGATGAAAAGATCAAAGAACCTACTCTGTTGGGTTTTCATACAGCTAGCGGGAAAAAAGTTAAAATTGCAAAGGAATCTTTGGACAAAGTGAAAAACCTTTTTGATGAAAAAGAGCAAGGTACTAGTGAAATCACCAGTTTTAGCCATCAATGGGCAAAGACCCTAAAGTACAGAGAGGCCTGTAAAGACCTTGAATTAGCATGTGAGACCATTGAGATCACAGCTGCCCCAAAGTGTAAAGAAATGCAGAATTCTCTCAATAATGATAAAAACCTTGTTTCTATTGAGACTGTGGTGCCACCTAAGCTCTTAAGTGATAATTTATGTAGACAAACTGAAAATCTCAAAACATCAAAAAGTATCTTTTTGAAAGTTAAAGTACATGAAAATGTAGAAAAAGAAACAGCAAAAAGTCCTGCAACTTGTTACACAAATCAGTCCCCTTATTCAGTCATTGAAAATTCAGCCTTAGCTTTTTACACAAGTTGTAGTAGAAAAACTTCTGTGAGTCAGACTTCATTACTTGAAGCAAAAAAATGGCTTAGAGAAGGAATATTTGATGGTCAACCAGAAAGAATAAATACTGCAGATTATGTAGGAAATTATTTGTATGAAAATAATTCAAACAGTACTATAGCTGAAAATGACAAAAATCATCTCTCCGAAAAACAAGATACTTATTTAAGTAACAGTAGCATGTCTAACAGCTATTCCTACCATTCTGATGAGGTATATAATGATTCAGGATATCTCTCAAAAAATAAACTTGATTCTGGTATTGAGCCAGTATTGAAGAATGTTGAAGATCAAAAAAACACTAGTTTTTCCAAAGTAATATCCAATGTAAAAGATGCAAATGCATACCCACAAACTGTAAATGAAGATATTTGCGTTGAGGAACTTGTGACTAGCTCTTCACCCTGCAAAAATAAAAATGCAGCCATTAAATTGTCCATATCTAATAGTAATAATTTTGAGGTAGGGCCACCTGCATTTAGGATAGCCAGTGGTAAAATCGTTTGTGTTTCACATGAAACAATTAAAAAAGTGAAAGACATATTTACAGACAGTTTCAGTAAAGTAATTAAGGAAAACAACGAGAATAAATCAAAAATTTGCCAAACGAAAATTATGGCAGGTTGTTACGAGGCATTGGATGATTCAGAGGATATTCTTCATAACTCTCTAGATAATGATGAATGTAGCACGCATTCACATAAGGTTTTTGCTGACATTCAGAGTGAAGAAATTTTACAACATAACCAAAATATGTCTGGATTGGAGAAAGTTTCTAAAATATCACCTTGTGATGTTAGTTTGGAAACTTCAGATATATGTAAATGTAGTATAGGGAAGCTTCATAAGTCAGTCTCATCTGCAAATACTTGTGGGATTTTTAGCACAGCAAGTGGAAAATCTGTCCAGGTATCAGATGCTTCATTACAAAACGCAAGACAAGTGTTTTCTGAAATAGAAGATAGTACCAAGCAAGTCTTTTCCAAAGTATTGTTTAAAAGTAACGAACATTCAGACCAGCTCACAAGAGAAGAAAATACTGCTATACGTACTCCAGAACATTTAATATCCCAAAAAGGCTTTTCATATAATGTGGTAAATTCATCTGCTTTCTCTGGATTTAGTACAGCAAGTGGAAAGCAAGTTTCCATTTTAGAAAGTTCCTTACACAAAGTTAAGGGAGTGTTAGAGGAATTTGATTTAATCAGAACTGAGCATAGTCTTCACTATTCACCTACGTCTAGACAAAATGTATCAAAAATACTTCCTCGTGTTGATAAGAGAAACCCAGAGCACTGTGTAAACTCAGAAATGGAAAAAACCTGCAGTAAAGAATTTAAATTATCAAATAACTTAAATGTTGAAGGTGGTTCTTCAGAAAATAATCACTCTATTAAAGTTTCTCCATATCTCTCTCAATTTCAACAAGACAAACAACAGTTGGTATTAGGAACCAAAGTCTCACTTGTTGAGAACATTCATGTTTTGGGAAAAGAACAGGCTTCACCTAAAAACGTAAAAATGGAAATTGGTAAAACTGAAACTTTTTCTGATGTTCCTGTGAAAACAAATATAGAAGTTTGTTCTACTTACTCCAAAGATTCAGAAAACTACTTTGAAACAGAAGCAGTAGAAATTGCTAAAGCTTTTATGGAAGATGATGAACTGACAGATTCTAAACTGCCAAGTCATGCCACACATTCTCTTTTTACATGTCCCGAAAATGAGGAAATGGTTTTGTCAAATTCAAGAATTGGAAAAAGAAGAGGAGAGCCCCTTATCTTAGTGGGAGAACCCTCAATCAAAAGAAACTTATTAAATGAATTTGACAGGATAATAGAAAATCAAGAAAAATCCTTAAAGGCTTCAAAAAGCACTCCAGATGGCACAATAAAAGATCGAAGATTGTTTATGCATCATGTTTCTTTAGAGCCGATTACCTGTGTACCCTTTCGCACAACTAAGGAACGTCAAGAGATACAGAATCCAAATTTTACCGCACCTGGTCAAGAATTTCTGTCTAAATCTCATTTGTATGAACATCTGACTTTGGAAAAATCTTCAAGCAATTTAGCAGTTTCAGGACATCCATTTTATCAAGTTTCTGCTACAAGAAATGAAAAAATGAGACACTTGATTACTACAGGCAGACCAACCAAAGTCTTTGTTCCACCTTTTAAAACTAAATCACATTTTCACAGAGTTGAACAGTGTGTTAGGAATATTAACTTGGAGGAAAACAGACAAAAGCAAAACATTGATGGACATGGCTCTGATGATAGTAAAAATAAGATTAATGACAATGAGATTCATCAGTTTAACAAAAACAACTCCAATCAAGCAGCAGCTGTAACTTTCACAAAGTGTGAAGAAGAACCTTTAGATTTAATTACAAGTCTTCAGAATGCCAGAGATATACAGGATATGCGAATTAAGAAGAAACAAAGGCAACGCGTCTTTCCACAGCCAGGCAGTCTGTATCTTGCAAAAACATCCACTCTGCCTCGAATCTCTCTGAAAGCAGCAGTAGGAGGCCAAGTTCCCTCTGCGTGTTCTCATAAACAGCTGTATACGTATGGCGTTTCTAAACATTGCATAAAAATTAACAGCAAAAATGCAGAGTCTTTTCAGTTTCACACTGAAGATTATTTTGGTAAGGAAAGTTTATGGACTGGAAAAGGAATACAGTTGGCTGATGGTGGATGGCTCATACCCTCCAATGATGGAAAGGCTGGAAAAGAAGAATTTTATAGGGCTCTGTGTGACACTCCAGGTGTGGATCCAAAGCTTATTTCTAGAATTTGGGTTTATAATCACTATAGATGGATCATATGGAAACTGGCAGCTATGGAATGTGCCTTTCCTAAGGAATTTGCTAATAGATGCCTAAGCCCAGAAAGGGTGCTTCTTCAACTAAAATACAGATATGATACGGAAATTGATAGAAGCAGAAGATCGGCTATAAAAAAGATAATGGAAAGGGATGACACAGCTGCAAAAACACTTGTTCTCTGTGTTTCTGACATAATTTCATTGAGCGCAAATATATCTGAAACTTCTAGCAATAAAACTAGTAGTGCAGATACCCAAAAAGTGGCCATTATTGAACTTACAGATGGGTGGTATGCTGTTAAGGCCCAGTTAGATCCTCCCCTCTTAGCTGTCTTAAAGAATGGCAGACTGACAGTTGGTCAGAAGATTATTCTTCATGGAGCAGAACTGGTGGGCTCTCCTGATGCCTGTACACCTCTTGAAGCCCCAGAATCTCTTATGTTAAAGATTTCTGCTAACAGTACTCGGCCTGCTCGCTGGTATACCAAACTTGGATTCTTTCCTGACCCTAGACCTTTTCCTCTGCCCTTATCATCGCTTTTCAGTGATGGAGGAAATGTTGGTTGTGTTGATGTAATTATTCAAAGAGCATACCCTATACAGTGGATGGAGAAGACATCATCTGGATTATACATATTTCGCAATGAAAGAGAGGAAGAAAAGGAAGCAGCAAAATATGTGGAGGCCCAACAAAAGAGACTAGAAGCCTTATTCACTAAAATTCAGGAGGAATTTGAAGAACATGAAGAAAACACAACAAAACCATATTTACCATCACGTGCACTAACAAGACAGCAAGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTGAAGAATGCAGCAGACCCAGCTTACCTTGAGGGTTATTTCAGTGAAGAGCAGTTAAGAGCCTTGAATAATCACAGGCAAATGTTGAATGATAAGAAACAAGCTCAGATCCAGTTGGAAATTAGGAAGGCCATGGAATCTGCTGAACAAAAGGAACAAGGTTTATCAAGGGATGTCACAACCGTGTGGAAGTTGCGTATTGTAAGCTATTCAAAAAAAGAAAAAGATTCAGTTATACTGAGTATTTGGCGTCCATCATCAGATTTATATTCTCTGTTAACAGAAGGAAAGAGATACAGAATTTATCATCTTGCAACTTCAAAATCTAAAAGTAAATCTGAAAGAGCTAACATACAGTTAGCAGCGACAAAAAAAACTCAGTATCAACAACTACCGGTTTCAGATGAAATTTTATTTCAGATTTACCAGCCACGGGAGCCCCTTCACTTCAGCAAATTTTTAGATCCAGACTTTCAGCCATCTTGTTCTGAGGTGGACCTAATAGGATTTGTCGTTTCTGTTGTGAAAAAAACAGGACTTGCCCCTTTCGTCTATTTGTCAGACGAATGTTACAATTTACTGGCAATAAAGTTTTGGATAGACCTTAATGAGGACATTATTAAGCCTCATATGTTAATTGCTGCAAGCAACCTCCAGTGGCGACCAGAATCCAAATCAGGCCTTCTTACTTTATTTGCTGGAGATTTTTCTGTGTTTTCTGCTAGTCCAAAAGAGGGCCACTTTCAAGAGACATTCAACAAAATGAAAAATACTGTTGAGAATATTGACATACTTTGCAATGAAGCAGAAAACAAGCTTATGCATATACTGCATGCAAATGATCCCAAGTGGTCCACCCCAACTAAAGACTGTACTTCAGGGCCGTACACTGCTCAAATCATTCCTGGTACAGGAAACAAGCTTCTGATGTCTTCTCCTAATTGTGAGATATATTATCAAAGTCCTTTATCACTTTGTATGGCCAAAAGGAAGTCTGTTTCCACACCTGTCTCAGCCCAGATGACTTCAAAGTCTTGTAAAGGGGAGAAAGAGATTGATGACCAAAAGAACTGCAAAAAGAGAAGAGCCTTGGATTTCTTGAGTAGACTGCCTTTACCTCCACCTGTTAGTCCCATTTGTACATTTGTTTCTCCGGCTGCACAGAAGGCATTTCAGCCACCAAGGAGTTGTGGCACCAAATACGAAACACCCATAAAGAAAAAAGAACTGAATTCTCCTCAGATGACTCCATTTAAAAAATTCAATGAAATTTCTCTTTTGGAAAGTAATTCAATAGCTGACGAAGAACTTGCATTGATAAATACCCAAGCTCTTTTGTCTGGTTCAACAGGAGAAAAACAATTTATATCTGTCAGTGAATCCACTAGGACTGCTCCCACCAGTTCAGAAGATTATCTCAGACTGAAACGACGTTGTACTACATCTCTGATCAAAGAACAGGAGAGTTCCCAGGCCAGTACGGAAGAATGTGAGAAAAATAAGCAGGACACAATTACAACTAAAAAATATATCTAAGCATTTGCAAAGGCGACAATAAATTATTGACGCTTAACCTTTCCAGTTTATAAGACTGGAATATAATTTCAAACCACACATTAGTACTTATGTTGCACAATGAGAAAAGAAATTAGTTTCAAATTTACCTCAGCGTTTGTGTATCGGGCAAAAATCGTTTTGCCCGATTCCGTATTGGTATACTTTTGCTTCAGTTGCATATCTTAAAACTAAATGTAATTTATTAACTAATCAAGAAAAACATCTTTGGCTGAGCTCGGTGGCTCATGCCTGTAATCCCAACACTTTGAGAAGCTGAGGTGGGAGGAGTGCTTGAGGCCAGGAGTTCAAGACCAGCCTGGGCAACATAGGGAGACCCCCATCTTTACGAAGAAAAAAAAAAAGGGGAAAAGAAAATCTTTTAAATCTTTGGATTTGATCACTACAAGTATTATTTTACAATCAACAAAATGGTCATCCAAACTCAAACTTGAGAAAATATCTTGCTTTCAAATTGACACTA

GGCTTTAAGTATCCATGGCTTTAAGTATCCATGGCTTTAAGTATCCATGGCTTTAAGTATCCAT

“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).

How do you get the bad gene?

BRCA Mutation Increases Breast and Ovarian Cancer Risks

AJHG 1995;56:265-271Science 2003: 643-646

JCO 2005 23 (8): 1656-63NCI 2005

20

40

60

80

100

Breast cancerby age 50

Breast cancerby age 70

Ovarian cancerby age 70

2%

Up to 50%

8%

Up to 87%

Ris

k of

Can

cer

(%

)

<1%

Up to 44%

General PopulationBRCA Mutation

Lancet 1994;343:692-695 NEJM 1997;336:1401-1408

AJHG 2003;72:1117-1130

BRCA Mutation Increases Risk of Second Breast Cancer

Lancet 1998;351:316-21JCO 2004;22:2328-35

Lancet 1994;3343:692-5Gynecol Oncol. 2005 Jan;96(1):222-6

0

20

40

60

Breast Cancerafter 5 years

Breast Cancer by age 70

Up to 3.5%

Up to 27%

Up to 11%

Up to 64%

Ris

k of

Can

cer

(%)

General PopulationBRCA Mutation

Ca Epi Biomarkers Prev. 1999;8(10):855-61JNCI 1999;15:1310-6

JCO 1998;16:2417-25

Risks in Men With a BRCA Mutation

JCO 2004;22: 735-42

NCI 2005

Breast Cancerby age 80

Prostate Cancerby age 80

General PopulationBRCA Mutation*

5

10

15

20

25

<1%

7%

15%

20%

Ris

k of

Can

cer

(%)

*Risks refer to BRCA2 mutation carriers.

Risks for male BRCA1 mutation carriers are less characterized

“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

“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.

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

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

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

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

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.

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.

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.

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.

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.

Family History & BRCA Positive and Negative

Ca

nce

r R

isks

%

50

Age (Years)30 50 70

Positive for deleteriousBRCA mutation

100

Risk based on family history

Negative for familialBRCA 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

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.

Managing Hereditary Cancer Risk

• Surveillance

• Chemoprevention

• Prophylactic surgery

*Individual risk reduction may vary based on personal health history

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

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;296:185-92Clin Oncol. 2005 Mar

10;23(8):1656-63NEJM 2002;346:1609-15

www.nccn.org

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.

Surveillance for Breast Cancer

www.nccn.orgCancer

2004;100:479-89NEJM 2004;351:427-

37

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

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.

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;356:1876-81JAMA 2001;286:2251-6JNCI 1998; 90:1371-88

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

Reconstruction after Mastectomy has come a long way

Postoperative left mastectomy – left latissimus flap and implant

Pre-operative view

Nipple Sparing Mastectomy

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

Laboratories, Inc.

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

-307

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.

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

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 Laboratories, Inc.

Rachel, age 40 – no cancer

Rachel’s Test result

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

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

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.

Heather, age 38

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

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.

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.

Questions?