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Personalized Breast Cancer Care

Personalized Breast Cancer Care. Sunil Patel, MD Medical Oncology and Hematology Collom and Carney Clinic. No financial disclosure. Personalized Breast Cancer Care Topics. Role of genetic/familial high risk assessment

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Personalized Breast Cancer Care

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  1. Personalized Breast Cancer Care Sunil Patel, MD Medical Oncology and Hematology Collom and Carney Clinic.

  2. No financial disclosure

  3. Personalized Breast Cancer CareTopics • Role of genetic/familial high risk assessment • Role of specific markers on breast tissue in decision making of treatment. • For some patients, more(=chemo) is not better. - Role of genetic profiling of the tumor in decision making.

  4. Breast Cancer Progress Report • Breast Cancer mortality rates have decreased by 2.3% annually since 1990 • The decline in mortality is primarily due to early detection and new treatmentmethods Source: Breast Cancer Facts and Figures 2005-2006 National Center for Health Statistics data as analyzed by NCI

  5. The Stages of Breast Cancer Breast Cancer is diagnosed according to stages (stages 0 through IV) under the TNM classification. Factors used in staging of Breast Cancer: • Tumor Size Size of primary tumor • Nodal statusIndicates presence or absence of cancer cells in lymph nodes • MetastasisIndicates if cancer cells have spread from the affected breast to other areas of the body (i.e. skin, liver, lungs, bone) Source:National Cancer Institute

  6. Genetics Help us Identify Patients at High Risk of Developing Breast Cancer Genetics • Genetics is the study of heredity • While genetics influence genomics, genetics is responsible for only 5-10% of breast cancer • Genetics focuses primarily on the likelihood of developingcancer • Genetic tests find mutations, not disease Source: Understanding Cancer Series: Gene Testing, National Cancer Institute

  7. Genomics Help us Look at the Patients Individual Tumor Biology • Genomics • Genomics is the study of how genes interact and are expressed as a whole • Genomics and gene expression profiling tools focus on the cancer itselfand can help determine • How aggressive is the cancer (prognosis) • What is the likely benefit from treatment (prediction)

  8. Examples of Genetic and Genomic Tests Genetic Test • BRCA1 and BRCA2 • The genetic make up of patients is tested for BRCA1 and BRCA2 mutations. Patients with those mutations have higher chances of developing breast cancer. Genomic Test • Oncotype DX® Breast Cancer Assay • The expression level of 21 genes is measured in tumor tissue from patients that have already been diagnosed with breast cancer. This assay evaluates if a patient is going to recur (prognostic) and predicts benefit from chemotherapy and hormonal therapy (predictive) • Mammaprint assay

  9. Genetic Risk Factor Assessment • NX 42 year old white female with no family history of breast cancer, now has 4 cm right breast cancer. • Biopsy confirmed IDC,ER+, HER2/neu + • What’s next? – Surgery- ipsilateral or bilateral mastectomy, chemo, hormonal therapy? Or more?

  10. Breast & Ovarian Cancer Risk Assessment – for patients • Age 50 y or younger • Triple negative breast cancer ( ER-PR-Her2/Neu-) • Two breast cancer primaries • Breast cancer at any age - 1 or more close relative with breast or ovarian cancer at age 50 or younger -2 or more close relatives with breast and/or pancreatic cancer -women of Ashkenazi Jewish descent at any age breast/ovarian cancer. • Other cancer history – Thyroid, sarcoma, adrenal , endometrial, pancreatic, brain cancer • Ovarian cancer • Male breast cancer.

  11. Patient NX • NX 42 year old white female with no family history of breast cancer, now has 4 cm right breast cancer. • Biopsy confirmed IDC,ER+, HER2/neu + • What’s next? – Surgery- ipsilateral or bilateral mastectomy, chemo, hormonal therapy? Or more?

  12. Patient NX • Should go I go for surgery first? Then chemo? • Blood for BRCA 1 and 2 mutation.

  13. Patient MB • MB is a 53 year old white male with right sided breast cancer, stage I.

  14. BReastCAncer Genes

  15. BReast CAncer • Women have about a 1 in 7 chance of getting breast cancer in their lifetime. • Most cancer is sporadic, about 5-10% of cases are genetically linked • Women inheriting mutation of BRCA gene have increased chance of disease • Also can lead to ovarian cancer

  16. The Numbers

  17. BRCA Genes • BRCA 1 and BRCA 2 • Roles they play

  18. Life is all about the right balance.

  19. What are they? • BRCA 1 and BRCA 2 • Known as breast and ovarian cancer susceptibility genes • Tumor suppressor genes • regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way • inhibit the growth of cells that line the milk ducts in the breast • Involved in many other functions including control of DNA replication and damage repair

  20. BRCA 1 • Cloned in 1994 (Miki etal) • Mapped to chromosome 17q21 • 5,592kb long • 24 exons

  21. BRCA 2 • Cloned in 1995 (Wooster etal.) • Mapped to chromosome 13q12-13 • 10,254 kb (3,418 aa) • 27 exons

  22. More Numbers

  23. Patient NX • BRCA 1 mutation positive • Neo-adjuvant chemotherapy then bilateral skin sparing mastectomy. • Hormonal therapy • Prophylactic bilateral salpingo-oopherectomy • Genetic counseling for family members.

  24. Patient MB • BRCA 2 mutation positive • Chemotherapy • Contra-lateral mastectomy • PSA screening test.

  25. Topics • Role of genetic/familial high risk assessment • Role of specific markers on breast tissue in decision making of treatment. • For some patients, more is not better. - Role of genetic profiling of the tumor in decision making.

  26. Tumor Size Lymph Node Status Age Tumor Grade AdjuvantOnline!Computer-based model ER/PRHER2 How Do We Assess Risk in Breast Cancer Patients? Classic Pathological Criteria

  27. ER/PR/Her2-Neu • Estrogen receptor • Progesterone receptor • Her2/Neu – Human epidermal growth factor Receptor 2 • ER/PR+ Her2/Neu – • ER/PR – Her2/Neu – (Triple negative) • ER/PR – Her2/Neu + • ER/PR+ Her2/Neu +

  28. Triple-Positive Breast Cancer ER-Pos HER2/neu-Pos H&E PR-Pos Triple-Negative Breast Cancer PR-Neg ER-Neg H&E HER2/neu-Neg

  29. Treatment options • Chemotherapy • Endocrine therapy – Tamoxifen or Aromatase inhibitor - Anastrozole (Arimidex) , Letrozole (Femara) , Exemestane (Aromasin) • Trastuzumab (Herceptin)

  30. HerceptinTM(trastuzumab)

  31. Triple negative breast cancerHormone Receptor - /HER2 - • Chemotherapy for tumor more than 0.5 cm. • Nodal involvement.

  32. Hormone Receptor Positive,HER2 Positive Breast Cancer • 0.5 cm or less tumor size – Adjuvant endocrine therapy • 0.6 to 1 cm – Adjuvant endocrine +/- chemo with trastuzumab. • > 1 cm tumor size and/or lymph node involvement – adjuvant endocrine therapy, chemotherapy with trastuzumab.

  33. Hormone Receptor Negative,HER2 Positive Breast Cancer • 0.5 cm or less tumor size – No chemo. • 0.6 to 1 cm – Consider chemo with trastuzumab. • > 1 cm tumor size and/or lymph node involvement – chemotherapy with trastuzumab. • HORMONAL THERAPY NOT USEFUL.

  34. Hormone Receptor Positive,HER2 Positive Breast Cancer • 0.5 cm or less tumor size – Adjuvant endocrine therapy • 0.6 to 1 cm – Adjuvant endocrine +/- chemo with trastuzumab. • > 1 cm tumor size and/or lymph node involvement – adjuvant endocrine therapy, chemotherapy with trastuzumab.

  35. Hormone Receptor Positive HER2 Negative Breast Cancer -Tumor size • Tumor size < 0.5 Cm and No LN involvement – Adjuvant endocrine therapy. No chemotherapy • T > 0.5 Cm and No LN involvement - adjuvant endocrine therapy +/- ?? Chemo.

  36. Hormone Receptor Positive HER2 Negative Breast Cancer • Nodal involvement > 2mm focus – adjuvant endocrine therapy + chemotherapy • 1 to 3 Lymph nodes or >3 nodes involved – does every one need chemo?

  37. Topics • Role of genetic/familial high risk assessment • Role of specific markers on breast tissue in decision making of treatment. • For some patients, more(=chemotherapy) is not better. - Role of genetic profiling of the tumor in decision making.

  38. New tools in the Genomic Era… Tumor Size Lymph Node Status Genetic Profiling of Tumor Age Tumor Grade ER/PRHER2 AdjuvantOnline!Computer-based model How Do We Assess Risk in Breast Cancer Patients? Classic Pathological Criteria

  39. Adjuvant Treatment for Early Stage Breast Cancer Today

  40. Hormonal Therapy Based on the Landmark NSABP B-14 Study using Tamoxifen If 100 women with ER+, N- disease are treated with hormonal therapyhow many will recur within 10 years? Fisher et al. N Engl J Med 1989;320(8):479-84

  41. Chemotherapy and Hormonal Therapy Based on the Landmark NSABP B-20 Study using Tamoxifen + Chemotherapy If all 100 women with ER+, N- disease are treated with chemotherapy and hormonal therapy, how many will benefit from the addition of chemotherapy? Fisher et al. J Natl Cancer Inst 1997;89:1673-82

  42. Outcomes of Adjuvant Chemotherapy in Breast Cancer Walgren et al. JCO 2005;23:7342-7349

  43. New tools in the Genomic Era… Tumor Size Lymph Node Status Genetic Profiling of Tumor Age Tumor Grade ER/PRHER2 AdjuvantOnline!Computer-based model How Do We Assess Risk in Breast Cancer Patients? Classic Pathological Criteria

  44. Patient A

  45. Patient B

  46. Patient C

  47. 5. Shared Decision Making 1. Patient’s tumor 2. Oncotype DX® Assay 4. Oncotype DX® Report 3. Analyze expression of tumor’s genes With Genomic Tools We Can Now Analyze Cancer at the Molecular Level

  48. Oncotype DX®: A Genomic Assay

  49. PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2 ESTROGEN ER PR Bcl2 SCUBE2 HER2 GRB7 HER2 REFERENCE Beta-actin GAPDH RPLPO GUS TFRC GSTM1 BAG1 INVASION Stromelysin 3 Cathepsin L2 CD68 Oncotype DX® 21-Gene Recurrence Score® (RS) Assay 16 Cancer and 5 Reference Genes From 3 Studies Paik et al. N Engl J Med. 2004;351: 2817-2826

  50. Oncotype DX® 21-Gene Recurrence Score® (RS) Assay Calculation of the Recurrence Score Result Paik et al. N Engl J Med. 2004;351: 2817-2826

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