Hereditary Factors in Breast Cancer Factores Hereditarios en C ncer de Seno

1. Hereditary Factors in Breast CancerFactores Hereditarios en Cáncer de Seno Jessica Ray, MS, CGC Genetic Counselor - Asesora en Genética Arizona Cancer Center Centro de Cáncer de Arizona Phone (520) 694-0800 jray@azcc.arizona.edu

2. OBJECTIVES  Introduce the field of genetic counseling Distinguish between sporadic, familial, and hereditary cancer Who should consider genetic counseling and genetic testing? Risks for cancers associated with genetic mutations Cost of genetic testing and insurance issues _________________________________________________________ OBJETIVOS Introducción del campo de asesoramiento en genética Diferencias entre el cáncer esporádico, familiar y hereditario ¿Quien debe de considerar asesoramiento en genética y pruebas genéticas? Riesgos de cáncer relacionados con mutaciones genéticas (versiones alteradas de genes) El costo de pruebas genéticas y problemas con el seguro médico

3. What is Genetic Counseling?  ¿ Qué es el Asesoramiento en Genética? Definition - Genetic counseling is the communication about medical and psychological issues associated with a genetic disorder in a family Focuses on hereditary cancer syndromes ------------------------------------------- Definición- Evaluación genética es el diálogo sobre asuntos médicos y psicológicos relacionados con un trastorno hereditario en una familia Se enfoca en síndromes de cánceres hereditarios

4. Why a Genetic Consultation? ¿Por qué tener Asesoramiento en Genética? To learn about Para aprender sobre - Personal risk - Riesgo personal - Children’s risk - Riesgo de los hijos - Family’s risk - Riesgo de los familiares Risks if have a “cancer gene” - Riesgo de tener un “gen canceroso” Screening - Evaluación precoz Surveillance - Vigilancia Treatment - Tratamiento Educational information Información educativa Genetic DNA testing Prueba genética de ADN

5. Sporadic, Familial or HereditaryCáncer Esporádico, Familiar y Hereditario 5-10% of cancers have a hereditary component de cánceres tienen un factor hereditario Hereditary Cancer Cáncer Hereditario - Younger age - Edad más temprana - Bilateral - Bilateral (ambos lados) Multifocal - Multifocal (más de un sitio) Most have an autosomal - La mayoría tienen patrón dominance dominante autosomático Non-inherited Factors Factores no Hereditarios - Early age first menses - Primera menstruación en edad temprana - No pregnancy - Ningún embarazo - Menopause at late age - Menopausia en edad avanzada - Hormone Replacement Therapy - Terapia de remplazo (HRT) hormonal

8. Key Flags that Warrant Genetic CounselingCaracterísticas Importantes que Justifican el Asesoramiento en Genética Family history: breast, ovarian, Historial familiar: seno, ovario, prostate, colon, melanoma, próstata, colon, melanoma , pancreatic, or other cancer type pancreático, u otro tipo de cáncer Cancer in every generation Cáncer en cada generación Early age at diagnosis (< 50 years) Diagnóstico en edad temprana Male breast cancer Cáncer de seno en el hombre Bilateral cancer or multiple Cáncer bilateral, o múltiple Family genetic mutation Mutación genética (genes de versión alterada) en la familia Ethnicity: Ashkenazi Jewish Etnicidad: Judia Ashkenazi

10. BRCA Mutation Increases Cancer RisksMutación de BRCA Aumenta los Riesgos de Cáncer Slide 7: A BRCA Mutation Increases the Risk of Early-Onset Breast Cancer Without intervention, the majority of women with inherited mutations in BRCA1 and BRCA2 will develop breast and/or ovarian cancer. The range of risks of breast and ovarian cancer associated with mutations in these genes has been characterized through numerous studies. The lower estimates of risk are derived from analysis of mutations in an unselected general population of individuals, whereas higher estimates of mutation-associated cancer risk are derived from families with a strong history of cancer. Generally, mutations in BRCA1 and BRCA2 are associated with a 45% to 87% risk of breast cancer by age 70. 1-3 Most importantly, hereditary breast cancer occurs at a far earlier age than the nonhereditary (sporadic) form. Women in the general population have only a 2% chance of developing breast cancer before age 50. However, a woman with a mutation in BRCA1 or BRCA2 has a 33% to 50% likelihood of developing breast cancer before reaching 50 years of age. 2,4 The risk of ovarian cancer due to inherited BRCA1 mutations is 28%1 to 44%2,3 by age 70, compared to the general population risk of 1%. Mutations in BRCA2 confer a risk of ovarian cancer of 11%to 27%3 by age 70, which represents up to a 15-fold increase compared to the general population. References: 1. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Breast Cancer Linkage Consortium: Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 2. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. NEJM 1997;336:1401-1408. 3. Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. AJHG 2003;72:1117-1130. 4. Easton DF, Ford D, Bishop DT, Breast Cancer Linkage Consortium: Breast and ovarian cancer incidence in BRCA1-mutation carriers. AJHG 1995;56:265-271. 5. King MC, Marks JH,Mandell JB. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science Oct 24 2003: 643-646. Slide 7: A BRCA Mutation Increases the Risk of Early-Onset Breast Cancer Without intervention, the majority of women with inherited mutations in BRCA1 and BRCA2 will develop breast and/or ovarian cancer. The range of risks of breast and ovarian cancer associated with mutations in these genes has been characterized through numerous studies. The lower estimates of risk are derived from analysis of mutations in an unselected general population of individuals, whereas higher estimates of mutation-associated cancer risk are derived from families with a strong history of cancer. Generally, mutations in BRCA1 and BRCA2 are associated with a 45% to 87% risk of breast cancer by age 70. 1-3 Most importantly, hereditary breast cancer occurs at a far earlier age than the nonhereditary (sporadic) form. Women in the general population have only a 2% chance of developing breast cancer before age 50. However, a woman with a mutation in BRCA1 or BRCA2 has a 33% to 50% likelihood of developing breast cancer before reaching 50 years of age. 2,4 The risk of ovarian cancer due to inherited BRCA1 mutations is 28%1 to 44%2,3 by age 70, compared to the general population risk of 1%. Mutations in BRCA2 confer a risk of ovarian cancer of 11%to 27%3 by age 70, which represents up to a 15-fold increase compared to the general population. References: 1. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Breast Cancer Linkage Consortium: Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 2. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. NEJM 1997;336:1401-1408. 3. Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. AJHG 2003;72:1117-1130. 4. Easton DF, Ford D, Bishop DT, Breast Cancer Linkage Consortium: Breast and ovarian cancer incidence in BRCA1-mutation carriers. AJHG 1995;56:265-271. 5. King MC, Marks JH,Mandell JB. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science Oct 24 2003: 643-646.

11. BRCA Mutation Increases Risk of a Second CancerMutación de BRCA Aumenta el Riesgo de Segundo Cáncer Slide 8 : A BRCA Mutation Increases the Risk of a Second Cancer Women who have developed breast cancer are at greatly increased risk of a second cancer if they carry a mutation in BRCA1 or BRCA2. Their risk of developing ovarian cancer is 10 times higher than women with early-onset breast cancer who do not have mutations, 1 or at least 16% in their lifetime.2 There are no current statistics for the general population. In addition, mutations in these genes greatly increase the risk of a second breast cancer.3-5 The risk of a contralateral breast cancer is increased up to 64% by age 70, 3 or 27.1% within five years of the initial diagnosis5 in women with BRCA1 mutations. Mutations in BRCA2 increase these risks to about 50% by age 70,4 or 23.5% within five years of the first breast cancer. 5 References: 1. Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. JCO 1998;16:2417-2425. 2. The Breast Cancer Linkage Consortium. Cancer Risks in BRCA2 Mutation Carriers. JNCI 1999;15:1310-1316. 3 Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 4. Verhoog LC, Brekelmans CTM, Seynaeve C, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998;351:316-321. 5. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. JCO 2004;22:2328-2335. Slide 8 : A BRCA Mutation Increases the Risk of a Second Cancer Women who have developed breast cancer are at greatly increased risk of a second cancer if they carry a mutation in BRCA1 or BRCA2. Their risk of developing ovarian cancer is 10 times higher than women with early-onset breast cancer who do not have mutations, 1 or at least 16% in their lifetime.2 There are no current statistics for the general population. In addition, mutations in these genes greatly increase the risk of a second breast cancer.3-5 The risk of a contralateral breast cancer is increased up to 64% by age 70, 3 or 27.1% within five years of the initial diagnosis5 in women with BRCA1 mutations. Mutations in BRCA2 increase these risks to about 50% by age 70,4 or 23.5% within five years of the first breast cancer. 5 References: 1. Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. JCO 1998;16:2417-2425. 2. The Breast Cancer Linkage Consortium. Cancer Risks in BRCA2 Mutation Carriers. JNCI 1999;15:1310-1316. 3 Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 4. Verhoog LC, Brekelmans CTM, Seynaeve C, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998;351:316-321. 5. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. JCO 2004;22:2328-2335.

12. Average Age of DiagnosisEdad Promedia Durante el Diagnóstico Hereditary Cancer Sporadic Cancer Cáncer Hereditario Cáncer Esporádico Breast - Seno 41 Breast - Seno 62 Ovarian - Ovario 40-50 Ovarian - Ovario 60 Prostate - Próstata 63 Prostate-Próstata 71

13. Risk Reduction OptionsOpciones Para Disminuir El Riesgo Surveillance Vigilancia Alternate Mammogram & Alternar el mamograma y breast MRI every 6 months la resonancia magnética del seno cada 6 meses Prophylactic Surgeries Cirugías Preventivas Bilateral or Unilateral Mastectomy La mastectomía de dos o un lado 90% reduction in breast cancer risk reduce el riesgo de cáncer de seno-90% Bilateral ovary removal La operación de los dos ovarios 96% reduction in ovarian cancer risk reduce el riesgo cáncer de ovarios-96% Prophylactic bilateral ovarian removal La cirugía preventiva – operación de before menopause los dos ovarios antes de la menopausia 50% reduction in breast cancer risk reduce el riesgo cáncer de seno-50% Chemoprevention Prevención de Quimioterapia Tamoxifen, Raloxifene Tamoxifeno, Raloxifeno

14. Genetic Testing - When?Pruebas de Genética - ¿Cuándo? American Society of Clinical Sociedad Americana de Oncología Oncology recommends offering Clínica, recomienda ofrecer las genetic testing … pruebas de genética… If personal or family history… Si hay historial personal o familiar… If test can be adequately interpreted… Si la prueba puede ser interpretada adecuadamente… If results will aid in diagnosis… Si los resultados ayudarían al diagnóstico… If results influences management of Si influenciarían el cuidado de pacientes y patient or family members with familiares con riesgo hereditario heredity risk of cancer de cáncer Do the genetic testing … Recomienda pruebas de genética only if before and after únicamente antes y después de genetic counseling including asesoramiento en genética, incluyendo discussion of possible risks and una discusión sobre posibles riesgos benefits of cancer early detection y los beneficios de detección precoz and prevention y prevención de cáncer

15. Genetic Testing  Pruebas de Genética - Not everyone with found BRCA1/2 mutation will develop cancer - Testing of minors: Preimplantation genetic diagnosis (PGD) - Difficult genetic test results Variants: 26% in Latinas - Insurance issues and costs ________________________________ - No todos los que tienen la mutación BRCA1/2 desarrollarán cáncer - Pruebas de menores: Diagnóstico genético antes del implante (PGD) - Resultados de pruebas de genética pueden ser difíciles de interpretar Variantes: 26 % en Latinas - Problemas de seguro médico y costo

16. BRCA1 & BRCA2 TestingPruebas de BRCA1 & BRCA2 Only at Myriad Genetic Laboratories Cost of full sequencing: $3,120 Cost if family mutation is known: $385 Únicamente en los Laboratorios Genéticos Myriad Costo completo: $3,120 Costo si la mutación familiar es identificada: $385

17. Health Insurance Issues  Problemas de Seguro Médico Genetic discrimination Laws to prevent discrimination GINA (Genetic Information Non-Discrimination Act) Genetic tests can provide life-saving information Discriminación basada en genética Leyes para prevenir la discriminación GINA (Acta no-discriminatoria de información genética) Pruebas genéticas pueden dar información que le pueda salvar la vida Fear of insurance discrimination is the number 1 reason why patients decline BRCA testing in the USFear of insurance discrimination is the number 1 reason why patients decline BRCA testing in the US

18. Implications Consecuencias Negative results, Resultados negativos, does not mean no risk no significa ningún riesgo Women at high risk Mujeres con riesgo elevado with no BRCA1/2 mutation sin mutación de BRCA 1/2 Need BRCA1/2 testing Se necesita ampliar la prueba expanded de BRCA1/2 Tests need to detect Las pruebas necesitan more breast cancer detectar más cáncer de seno Need more research Se necesitan más investigación to find other genes para identificar otros genes resposible for breast cancer que son responsables por el cáncer de seno

19. Hereditary Factors in Breast CancerFactores Hereditarios en Cáncer de Seno Jessica Ray, MS, CGC Phone (520) 694-0800 jray@azcc.arizona.edu