Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Genetic assays in breast cancer

Role of genetic assays to predict the role of chemotherapy in treatment of breast cancer

  • Login to see the comments

Genetic assays in breast cancer

  1. 1. Dr. Vibhay Pareek GENETIC ASSAYS IN BREAST CANCER
  2. 2. PROGNOSTIC AND PREDICTIVE MARKERS:
  3. 3. • Axillary node status • Histological grade • Tumor size • Patient age • LVI • ER/PR status • Her2 Neu Status • Mammaprint • Oncotype DX PROGNOSTIC OR RECURRENCE RISK These markers estimate risk of disease recurrence
  4. 4. • ER Status • Her2 Neu Status • Oncotype DX test PREDICTIVE (TREATMENT BENEFITS)
  5. 5. THE QUESTION IS WHY IS IT NEEDED ……
  6. 6. • Several tests are available to help improve the prediction of patient survival upon diagnosis of breast cancer. • These prognostic tests assist the decision-making process for cancer treatment by allowing physicians to identify patients who are at low risk of recurrence. • The currently available tests examine the activity levels of 16 to 70 genes.
  7. 7. • Oncotype DX • MammaPrint • Mammostrat • Prosigna GENOMIC ASSAYS AVAILABLE
  8. 8. • Estimate a woman’s risk of recurrence of early-stage, hormone- receptor-positive breast cancer, as well as how likely she is to benefit from chemotherapy after breast cancer surgery • Estimate a woman’s recurrence risk of DCIS (ductal carcinoma in situ) and/or the risk of a new invasive cancer developing in the same breast, as well as how likely she is to benefit from radiation therapy after DCIS surgery • Analyzes the activity of 21 genes and then calculates a recurrence score number between 0 and 100; the higher the score, the greater the risk of recurrence. ONCOTYPE DX
  9. 9. • Estimate a women’s recurrence risk for early-stage breast cancer • The breast cancer can be hormone-receptor-positive or hormone-receptor-negative • Analyzes 70 genes to see how active they are and then calculates either a high-risk or a low-risk recurrence score • MammaPrint results can help a woman and her doctor make a more informed decision about whether to use chemotherapy to reduce recurrence risk MAMMAPRINT
  10. 10. • Estimate a woman’s risk of recurrence of early-stage, hormone-receptor-positive breast cancer • Measures the levels of five genes in breast cancer cells • Calculate a risk index score • The higher the risk index, the more likely the cancer is to come back • Women are assigned to a risk category (high, moderate, or low) based on their risk index score. MAMMOSTRAT
  11. 11. • Analyzes the activity of 58 genes and calculates a risk of recurrence score (low, intermediate, or high) • Research suggests the Prosigna assay eventually may be used more frequently to make treatment decisions based on the risk of distant recurrence (cancer coming back in a part of the body away from the breast) within 10 years of diagnosis of early-stage hormone-receptor positive disease with up to three positive lymph nodes after 5 years of hormonal therapy treatment in postmenopausal women PROSIGNA ASSAY
  12. 12. • The Oncotype DX test is a genomic test that analyzes the activity of a group of genes that can affect how a cancer is likely to behave and respond to treatment. • The Oncotype DX test is the only one of the four genomic tests for breast cancer (MammaPrint, Mammostrat, and Prosigna are the others) with results that have been validated with much vigorous research
  13. 13. • The Oncotype DX is used in two ways: – to help doctors figure out a woman’s risk of early-stage, ER +ve breast cancer coming back (recurrence), as well as how likely she is to benefit from chemotherapy after breast cancer surgery – to help doctors figure out a woman’s risk of DCIS (ductal carcinoma in situ) coming back (recurrence) and/or the risk of a new invasive cancer developing in the same breast, as well as how likely she is to benefit from radiation therapy after DCIS surgery
  14. 14. • Because strong results are available and the Oncotype DX test is included in the NCCN and ASCO treatment guidelines, it is the only genomic breast cancer test widely used to make treatment decisions. • The results of the Oncotype DX test, combined with other features of the cancer, can help you make a more informed decision about whether or not to have chemotherapy to treat early-stage hormone-receptor-positive breast cancer or radiation therapy to treat DCIS.
  15. 15. • you’ve recently been diagnosed with stage I or II invasive breast cancer • the cancer is estrogen-receptor-positive • there is no cancer in your lymph nodes (lymph node-negative breast cancer) • you and your doctor are making decisions about chemotherapy • you’ve recently been diagnosed with DCIS • you’re having lumpectomy to remove the DCIS ELIGIBILITY FOR THE TEST:
  16. 16. HOW DOES ONCOTYPE DX WORK:
  17. 17. • The Oncotype DX genomic test analyzes the activity of 21 genes that can influence how likely a cancer is to grow and respond to treatment. • Looking at these 21 genes can provide specific information on: – the likelihood that the breast cancer will return – whether you’re likely to benefit from chemotherapy if you’re being treated for early-stage invasive breast cancer – whether you’re likely to benefit from radiation therapy if you’re being treated for DCIS
  18. 18. • Oncotype DX test results assign a Recurrence Score — a number between 0 and 100 — to the early-stage breast cancer or DCIS – Recurrence Score lower than 18: low risk of recurrence. The benefit of chemotherapy for is likely to be small and will not outweigh the risks of side effects. – Recurrence Score of 18 up to and including 30: The cancer has an intermediate risk of recurrence. It’s unclear whether the benefits of chemotherapy outweigh the risks of side effects. – Recurrence Score greater than or equal to 31: The cancer has a high risk of recurrence, and the benefits of chemotherapy are likely to be greater than the risks of side effects.
  19. 19. • Recurrence Score lower than 39: The DCIS has a low risk of recurrence. The benefit of radiation therapy is likely to be small and will not outweigh the risks of side effects. • Recurrence Score between 39 and 54: The DCIS has an intermediate risk of recurrence. It’s unclear whether the benefits of radiation therapy outweigh the risks of side effects. • Recurrence Score greater than 54: The DCIS has a high risk of recurrence, and the benefits of radiation therapy are likely to be greater than the risks of side effects.
  20. 20. We will consider the Recurrence Score in combination with other factors, such as the size and grade of the cancer, the number of hormone receptors the cancer cells have (many versus few), and your age. Together, the decision about whether or not you should have chemotherapy or radiation therapy can be made.
  21. 21. LEVELS OF GENE EXPRESSION DETERMINE RECURRENCE SCORE 21-gene assay = 16 outcome-related genes + 5 reference genes Higher expression levels of “favorable” genes = ↓ RS Higher expression levels of “unfavorable” genes = ↑ RS A risk score is calculated from 0 -100 Cutoff points chosen based on Results of NSABP trial B-20
  22. 22. Results: Population distribution by Oncotype DX risk group A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer Intermed. risk 27.0% Low risk 51.0% Paik .S. et al. N Engl J Med 2004;351:2817-26 High risk 22.0%
  23. 23. All patients Low Risk (RS < 18) Years 100 0 20 40 60 DRFS(%) 80 0 2 6 104 8 12 1614 Intermediate Risk (RS 18 - 30) High Risk (RS  31) P < 0.00001 DISTANT RECURRENCE-FREE SURVIVAL (%) Paik .S. et al. N Engl J Med 2004;351:2817-26 93% 69%
  24. 24. Recurrence Score 40 35 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 45 50 Recurrence Score RateofDistantRecurrenceat10years 95% C.I. Recurrence Rate Low RS < 18 Rec. Rate = 6.8% C.I. = 4.0% - 9.6% Intermediate RS 18 - 31 Rec. Rate = 14.3% C.I. = 8.3% - 20.3% High RS  31 Rec. Rate = 30.5% C.I. = 23.6% - 37.4% Paik .S. et al. N Engl J Med 2004;351:2817-26
  25. 25. PROSPECTIVE VALIDATION OF ONCOTYPE DX:TAILORX TRIAL Low RS: Hormonal Therapy High RS: Chemo + Hormonal Therapy Hormonal Therapy Chemo + Hormonal 11,248 ER+/LN- patients
  26. 26. Low RS associated with minimal chemotherapy benefit High RS associated with large chemotherapy benefit The Oncotype DX Recurrence Score provides precise, quantitative information for individual patients on prognosis across and statistically independent of information on patient age, tumor size, and tumor grade. CONCLUSION:
  27. 27. High gradeLow grade High riskLow riskMammaPrint OLD VERSUS NEW DIAGNOSTICS OF CANCER: FROM MICROSCOPE TO MICROARRAY
  28. 28. • The MammaPrint test, made by Agendia, is a genomic test that analyzes the activity of certain genes in early-stage breast cancer. • Used to help make treatment decisions based on the cancer's risk of coming back (recurrence) within 10 years after diagnosis. • Knowing if a woman has a high or low risk of early-stage breast cancer coming back might help women and their doctors decide if chemotherapy or other treatments to reduce risk after surgery are needed.
  29. 29. • stage I or stage II • invasive • smaller than 5 centimeters • estrogen-receptor-positive or -negative • in three or fewer lymph nodes ELIGIBILITY:
  30. 30. • The MammaPrint test can be performed on fresh or freshly frozen breast cancer tissue or tissue that has been treated or "fixed" with a special solution to preserve the genetic material. • The MammaPrint test also can be done on a sample of preserved tissue that was removed during the original biopsy or surgery.
  31. 31. • The MammaPrint test looks at the activity of 70 genes and then calculates a recurrence score that is either low risk or high risk • Factors include: – age – size of the cancer – cancer grade – whether cancer cells were found in nearby lymph nodes – general health
  32. 32. PROGNOSIS CLASSIFIER FOR BREAST CANCER BASED ON GENOMIC PROFILING Good signature Poor signature threshold Rows:70 significant prognosisgenes Columns: tumor samples Threshold set with 10% false negatives 91% sensitivity; 73% specificity Metastases: white = +
  33. 33. RASTER TRIAL: AN IMPLEMENTATION STUDY
  34. 34. • The Mammostrat test, made by Clarient Diagnostic Services, is a genomic test that measures the levels of five certain genes in early-stage, hormone-receptor-positive breast cancer cells • Research suggests the Mammostrat test eventually may be widely used to help make treatment decisions based on whether the cancer has a lower or high risk of coming back (recurrence).
  35. 35. • Mammostrat can be used to analyze early-stage, hormone-receptor- positive breast cancers. • Stage I and stage II cancers are early-stage cancers. • The Mammostrat test is performed on preserved tissue that was removed during the original biopsy or surgery. ELIGIBILITY:
  36. 36. • The Prosigna Breast Cancer Prognostic Gene Signature Assay (formerly called the PAM50 test), made by NanoString, is a genomic test that analyzes the activity of certain genes in early-stage hormone-receptor-positive breast cancer.
  37. 37. • Research suggests the test may eventually be widely used to help make treatments decisions based on the risk of distant recurrence for postmenopausal women within 10 years of diagnosis of early-stage hormone-receptor positive disease with up to three positive lymph nodes after 5 years of hormonal therapy treatment.
  38. 38. • Knowing if a woman has a high or low risk of distant recurrence more than 5 years after diagnosis may be able to help doctors figure out whether 5 years or 10 years of hormonal therapy is better for her situation. • Research has shown that taking tamoxifen for 10 years instead of 5 years can better lower the risk of recurrence and improve overall survival for many women. • But if doctors knew that a woman had a low risk of distant recurrence, they might be able spare her the extra 5 years of hormonal therapy treatment.
  39. 39. • stage I or stage II and lymph node-negative • stage II with one to three positive nodes • hormone-receptor-positive • invasive • have been treated with surgery and hormonal therapy ELIGIBILITY:
  40. 40. • The Prosigna assay looks at the activity of 58 genes (called the PAM50 gene signature) to estimate the risk of distant recurrence of hormone-receptor-positive breast cancer from 5 to 10 years after diagnosis after 5 years of hormonal therapy treatment in postmenopausal women.
  41. 41. • Based on these activity levels, Prosigna assay results are reported as a risk of recurrence (ROR) score from 0 to 100 in two ways: – node-negative cancers are classified as low (0-40), intermediate (41-60), or high (61-100) risk – node-positive cancers are classified as low (0-40) or high (41-100) risk
  42. 42. SUMMARY
  43. 43. CONCLUSIONS • Gene signatures augment current clinicopathological variables in assessing risk of recurrence • Gene expression profiles may be both prognostic and predictive for patients with early breast cancer • NCCN guidelines suggest that Oncotype DX is an option for risk evaluation in 0.6-1 cm tumors with unfavorable characteristics or in >1 cm LN-, ER+/HER2 negative tumors
  44. 44. NCCN GUIDELINES INCLUDE ONCOTYPE DX® TESTING IN THE TREATMENT- DECISION PATHWAY FOR NODE-NEGATIVE AND MICROMETASTATIC DISEASE • Tumor 0.6-1.0 cm, moderately or poorly differentiated, intermediate or high grade, or vascular invasion • Tumor > 1 cm with favorable or unfavorable pathologic features Consider Oncotype DX Hormone receptor-positive, HER2-negative disease pT1, pT2, or pT3 and pN1mi No test RS < 18 RS 18- 30 RS ≥ 31 Adjuvant endocrine therapy ± adjuvant chemotherapy Adjuvant endocrine therapy endocrine therapy ± adjuvant chemotherapy Adjuvant endocrine therapy + adjuvant chemotherapy

×